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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Roles of Microglia in AD Pathology

Author(s): Gao Rong, Wu Hongrong, Li Qingqi and Zhao Jianfeng*

Volume 19, Issue 13, 2022

Published on: 13 February, 2023

Page: [854 - 869] Pages: 16

DOI: 10.2174/1567205020666230203112351

Price: $65

Open Access Journals Promotions 2
Abstract

Amyloid plaques and neurofibrillary tangles are two main characteristics of Alzheimer’s disease (AD). As cerebral resident phagocytes, microglia have different roles in Aβ pathology and tau pathology. In this review, we discuss microglial functions in the formation, clearance, and spread of Aβ and tau. Many receptors and enzymes, which are related to microglia, participate in AD pathologies and thus are thought to be potential targets of AD. So, making use of microglia can be beneficial to confine AD pathologies. To sum up, this article review the roles of microglia in AD pathology and possible corresponding treatments.

Keywords: Alzheimer’s disease, microglia, amyloid β, tau, neurofibrillary tangles, phagocytes.

[1]
Nichols, E.; Steinmetz, J.D.; Vollset, S.E.; Fukutaki, K.; Chalek, J.; Abd-Allah, F.; Abdoli, A.; Abualhasan, A.; Abu-Gharbieh, E.; Akram, T.T.; Al Hamad, H.; Alahdab, F.; Alanezi, F.M.; Alipour, V.; Almustanyir, S.; Amu, H.; Ansari, I.; Arabloo, J.; Ashraf, T.; Astell-Burt, T.; Ayano, G.; Ayuso-Mateos, J.L.; Baig, A.A.; Barnett, A.; Barrow, A.; Baune, B.T.; Béjot, Y.; Bezabhe, W.M.M.; Bezabih, Y.M.; Bhagavathula, A.S.; Bhaskar, S.; Bhattacharyya, K.; Bijani, A.; Biswas, A.; Bolla, S.R.; Boloor, A.; Brayne, C.; Brenner, H.; Burkart, K.; Burns, R.A.; Cámera, L.A.; Cao, C.; Carvalho, F.; Castro-de-Araujo, L.F.S.; Catalá-López, F.; Cerin, E.; Chavan, P.P.; Cherbuin, N.; Chu, D-T.; Costa, V.M.; Couto, R.A.S.; Dadras, O.; Dai, X.; Dandona, L.; Dandona, R.; De la Cruz-Góngora, V.; Dhamnetiya, D.; Dias da Silva, D.; Diaz, D.; Douiri, A.; Edvardsson, D.; Ekholuenetale, M.; El Sayed, I.; El-Jaafary, S.I.; Eskandari, K.; Eskandarieh, S.; Esmaeilnejad, S.; Fares, J.; Faro, A.; Farooque, U.; Feigin, V.L.; Feng, X.; Fereshtehnejad, S-M.; Fernandes, E.; Ferrara, P.; Filip, I.; Fillit, H.; Fischer, F.; Gaidhane, S.; Galluzzo, L.; Ghashghaee, A.; Ghith, N.; Gialluisi, A.; Gilani, S.A.; Glavan, I-R.; Gnedovskaya, E.V.; Golechha, M.; Gupta, R.; Gupta, V.B.; Gupta, V.K.; Haider, M.R.; Hall, B.J.; Hamidi, S.; Hanif, A.; Hankey, G.J.; Haque, S.; Hartono, R.K.; Hasaballah, A.I.; Hasan, M.T.; Hassan, A.; Hay, S.I.; Hayat, K.; Hegazy, M.I.; Heidari, G.; Heidari-Soureshjani, R.; Herteliu, C.; Househ, M.; Hussain, R.; Hwang, B-F.; Iacoviello, L.; Iavicoli, I.; Ilesanmi, O.S.; Ilic, I.M.; Ilic, M.D.; Irvani, S.S.N.; Iso, H.; Iwagami, M.; Jabbarinejad, R.; Jacob, L.; Jain, V.; Jayapal, S.K.; Jayawardena, R.; Jha, R.P.; Jonas, J.B.; Joseph, N.; Kalani, R.; Kandel, A.; Kandel, H.; Karch, A.; Kasa, A.S.; Kassie, G.M.; Keshavarz, P.; Khan, M.A.B.; Khatib, M.N.; Khoja, T.A.M.; Khubchandani, J.; Kim, M.S.; Kim, Y.J.; Kisa, A.; Kisa, S.; Kivimäki, M.; Koroshetz, W.J.; Koyanagi, A.; Kumar, G.A.; Kumar, M.; Lak, H.M.; Leonardi, M.; Li, B.; Lim, S.S.; Liu, X.; Liu, Y.; Logroscino, G.; Lorkowski, S.; Lucchetti, G.; Lutzky Saute, R.; Magnani, F.G.; Malik, A.A.; Massano, J.; Mehndiratta, M.M.; Menezes, R.G.; Meretoja, A.; Mohajer, B.; Mohamed Ibrahim, N.; Mohammad, Y.; Mohammed, A.; Mokdad, A.H.; Mondello, S.; Moni, M.A.A.; Moniruzzaman, M.; Mossie, T.B.; Nagel, G.; Naveed, M.; Nayak, V.C.; Neupane Kandel, S.; Nguyen, T.H.; Oancea, B.; Otstavnov, N.; Otstavnov, S.S.; Owolabi, M.O.; Panda-Jonas, S.; Pashazadeh Kan, F.; Pasovic, M.; Patel, U.K.; Pathak, M.; Peres, M.F.P.; Perianayagam, A.; Peterson, C.B.; Phillips, M.R.; Pinheiro, M.; Piradov, M.A.; Pond, C.D.; Potashman, M.H.; Pottoo, F.H.; Prada, S.I.; Radfar, A.; Raggi, A.; Rahim, F.; Rahman, M.; Ram, P.; Ranasinghe, P.; Rawaf, D.L.; Rawaf, S.; Rezaei, N.; Rezapour, A.; Robinson, S.R.; Romoli, M.; Roshandel, G.; Sahathevan, R.; Sahebkar, A.; Sahraian, M.A.; Sathian, B.; Sattin, D.; Sawhney, M.; Saylan, M.; Schiavolin, S.; Seylani, A.; Sha, F.; Shaikh, M.A.; Shaji, K.S.; Shannawaz, M.; Shetty, J.K.; Shigematsu, M.; Shin, J.I.; Shiri, R.; Silva, D.A.S.; Silva, J.P.; Silva, R.; Singh, J.A.; Skryabin, V.Y.; Skryabina, A.A.; Smith, A.E.; Soshnikov, S.; Spurlock, E.E.; Stein, D.J.; Sun, J.; Tabarés-Seisdedos, R.; Thakur, B.; Timalsina, B.; Tovani-Palone, M.R.; Tran, B.X.; Tsegaye, G.W.; Valadan Tahbaz, S.; Valdez, P.R.; Venketasubramanian, N.; Vlassov, V.; Vu, G.T.; Vu, L.G.; Wang, Y.-P.; Wimo, A.; Winkler, A.S.; Yadav, L.; Yahyazadeh Jabbari, S.H.; Yamagishi, K.; Yang, L.; Yano, Y.; Yonemoto, N.; Yu, C.; Yunusa, I.; Zadey, S.; Zastrozhin, M.S.; Zastrozhina, A.; Zhang, ZJ.; Murray, C.J.L.; Vos, T. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health, 2022, 7(2), e105-e125.
[http://dx.doi.org/10.1016/S2468-2667(21)00249-8] [PMID: 34998485]
[2]
Takashima, A.; Noguchi, K.; Sato, K.; Hoshino, T.; Imahori, K. Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity. Proc. Natl. Acad. Sci. USA, 1993, 90(16), 7789-7793.
[http://dx.doi.org/10.1073/pnas.90.16.7789] [PMID: 8356085]
[3]
Alvarez, A.; Toro, R.; Cáceres, A.; Maccioni, R.B. Inhibition of tau phosphorylating protein kinase cdk5 prevents β-amyloid-induced neuronal death. FEBS Lett., 1999, 459(3), 421-426.
[http://dx.doi.org/10.1016/S0014-5793(99)01279-X] [PMID: 10526177]
[4]
Streit, W.J.; Braak, H.; Del Tredici, K.; Leyh, J.; Lier, J.; Khoshbouei, H.; Eisenlöffel, C.; Müller, W.; Bechmann, I. Microglial activation occurs late during preclinical Alzheimer’s disease. Glia, 2018, 66(12), 2550-2562.
[http://dx.doi.org/10.1002/glia.23510] [PMID: 30417428]
[5]
Prinz, M.; Masuda, T.; Wheeler, M.A.; Quintana, F.J. Microglia and central nervous system–associated macrophages—from origin to disease modulation. Annu. Rev. Immunol., 2021, 39(1), 251-277.
[http://dx.doi.org/10.1146/annurev-immunol-093019-110159] [PMID: 33556248]
[6]
Boche, D.; Perry, V.H.; Nicoll, J.A.R. Review: Activation patterns of microglia and their identification in the human brain. Neuropathol. Appl. Neurobiol., 2013, 39(1), 3-18.
[http://dx.doi.org/10.1111/nan.12011] [PMID: 23252647]
[7]
Hickman, S.; Izzy, S.; Sen, P.; Morsett, L.; El Khoury, J. Microglia in neurodegeneration. Nat. Neurosci., 2018, 21(10), 1359-1369.
[http://dx.doi.org/10.1038/s41593-018-0242-x] [PMID: 30258234]
[8]
DiSabato, D.J.; Quan, N.; Godbout, J.P. Neuroinflammation: The devil is in the details. J. Neurochem., 2016, 139(Suppl. 2), 136-153.
[http://dx.doi.org/10.1111/jnc.13607] [PMID: 26990767]
[9]
Moyse, E.; Krantic, S.; Djellouli, N.; Roger, S.; Angoulvant, D.; Debacq, C.; Leroy, V.; Fougere, B.; Aidoud, A. Neuroinflammation: A possible link between chronic vascular disorders and neurodegenerative diseases. Front. Aging Neurosci., 2022, 14, 827263.
[http://dx.doi.org/10.3389/fnagi.2022.827263] [PMID: 35663580]
[10]
Krasemann, S.; Madore, C.; Cialic, R.; Baufeld, C.; Calcagno, N.; El Fatimy, R.; Beckers, L.; O’Loughlin, E.; Xu, Y.; Fanek, Z.; Greco, D.J.; Smith, S.T.; Tweet, G.; Humulock, Z.; Zrzavy, T.; Conde-Sanroman, P.; Gacias, M.; Weng, Z.; Chen, H.; Tjon, E.; Mazaheri, F.; Hartmann, K.; Madi, A.; Ulrich, J.D.; Glatzel, M.; Worthmann, A.; Heeren, J.; Budnik, B.; Lemere, C.; Ikezu, T.; Heppner, F.L.; Litvak, V.; Holtzman, D.M.; Lassmann, H.; Weiner, H.L.; Ochando, J.; Haass, C.; Butovsky, O. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity, 2017, 47(3), 566-581.e9.
[http://dx.doi.org/10.1016/j.immuni.2017.08.008] [PMID: 28930663]
[11]
Dani, M.; Wood, M.; Mizoguchi, R.; Fan, Z.; Walker, Z.; Morgan, R.; Hinz, R.; Biju, M.; Kuruvilla, T.; Brooks, D.J.; Edison, P. Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease. Brain, 2018, 141(9), 2740-2754.
[http://dx.doi.org/10.1093/brain/awy188] [PMID: 30052812]
[12]
Lee, M.; McGeer, E.; McGeer, P.L. Activated human microglia stimulate neuroblastoma cells to upregulate production of beta amyloid protein and tau: Implications for Alzheimer’s disease pathogenesis. Neurobiol. Aging, 2015, 36(1), 42-52.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.024] [PMID: 25169677]
[13]
Spangenberg, E.; Severson, P.L.; Hohsfield, L.A.; Crapser, J.; Zhang, J.; Burton, E.A.; Zhang, Y.; Spevak, W.; Lin, J.; Phan, N.Y.; Habets, G.; Rymar, A.; Tsang, G.; Walters, J.; Nespi, M.; Singh, P.; Broome, S.; Ibrahim, P.; Zhang, C.; Bollag, G.; West, B.L.; Green, K.N. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat. Commun., 2019, 10(1), 3758.
[http://dx.doi.org/10.1038/s41467-019-11674-z] [PMID: 31434879]
[14]
Baik, S.H.; Kang, S.; Son, S.M.; Mook-Jung, I. Microglia contributes to plaque growth by cell death due to uptake of amyloid β in the brain of Alzheimer’s disease mouse model. Glia, 2016, 64(12), 2274-2290.
[http://dx.doi.org/10.1002/glia.23074] [PMID: 27658617]
[15]
Venegas, C.; Kumar, S.; Franklin, B.S.; Dierkes, T.; Brinkschulte, R.; Tejera, D.; Vieira-Saecker, A.; Schwartz, S.; Santarelli, F.; Kummer, M.P.; Griep, A.; Gelpi, E.; Beilharz, M.; Riedel, D.; Golenbock, D.T.; Geyer, M.; Walter, J.; Latz, E.; Heneka, M.T. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease. Nature, 2017, 552(7685), 355-361.
[http://dx.doi.org/10.1038/nature25158] [PMID: 29293211]
[16]
Condello, C.; Yuan, P.; Schain, A.; Grutzendler, J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nat. Commun., 2015, 6(1), 6176.
[http://dx.doi.org/10.1038/ncomms7176] [PMID: 25630253]
[17]
Yuan, P.; Condello, C.; Keene, C.D.; Wang, Y.; Bird, T.D.; Paul, S.M.; Luo, W.; Colonna, M.; Baddeley, D.; Grutzendler, J. TREM2 Haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron, 2016, 90(4), 724-739.
[http://dx.doi.org/10.1016/j.neuron.2016.05.003] [PMID: 27196974]
[18]
Wang, Y.; Ulland, T.K.; Ulrich, J.D.; Song, W.; Tzaferis, J.A.; Hole, J.T.; Yuan, P.; Mahan, T.E.; Shi, Y.; Gilfillan, S.; Cella, M.; Grutzendler, J.; DeMattos, R.B.; Cirrito, J.R.; Holtzman, D.M.; Colonna, M. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med., 2016, 213(5), 667-675.
[http://dx.doi.org/10.1084/jem.20151948] [PMID: 27091843]
[19]
Moelgg, K.; Jummun, F.; Humpel, C. Spreading of beta-amyloid in organotypic mouse brain slices and microglial elimination and effects on cholinergic neurons. Biomolecules, 2021, 11(3), 434.
[http://dx.doi.org/10.3390/biom11030434] [PMID: 33804246]
[20]
Grubman, A.; Choo, X.Y.; Chew, G.; Ouyang, J.F.; Sun, G.; Croft, N.P.; Rossello, F.J.; Simmons, R.; Buckberry, S.; Landin, D.V.; Pflueger, J.; Vandekolk, T.H.; Abay, Z.; Zhou, Y.; Liu, X.; Chen, J.; Larcombe, M.; Haynes, J.M.; McLean, C.; Williams, S.; Chai, S.Y.; Wilson, T.; Lister, R.; Pouton, C.W.; Purcell, A.W.; Rackham, O.J.L.; Petretto, E.; Polo, J.M. Transcriptional signature in microglia associated with Aβ plaque phagocytosis. Nat. Commun., 2021, 12(1), 3015.
[http://dx.doi.org/10.1038/s41467-021-23111-1] [PMID: 34021136]
[21]
Hickman, S.E.; Allison, E.K.; El Khoury, J. Microglial dysfunction and defective beta-amyloid clearance pathways in aging Alzheimer’s disease mice. J. Neurosci., 2008, 28(33), 8354-8360.
[http://dx.doi.org/10.1523/JNEUROSCI.0616-08.2008] [PMID: 18701698]
[22]
Huang, Y.; Happonen, K.E.; Burrola, P.G.; O’Connor, C.; Hah, N.; Huang, L.; Nimmerjahn, A.; Lemke, G. Microglia use TAM receptors to detect and engulf amyloid β plaques. Nat. Immunol., 2021, 22(5), 586-594.
[http://dx.doi.org/10.1038/s41590-021-00913-5] [PMID: 33859405]
[23]
Takahashi, K.; Rochford, C.D.P.; Neumann, H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J. Exp. Med., 2005, 201(4), 647-657.
[http://dx.doi.org/10.1084/jem.20041611] [PMID: 15728241]
[24]
Yeh, F.L.; Wang, Y.; Tom, I.; Gonzalez, L.C.; Sheng, M. TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid-beta by microglia. Neuron, 2016, 91(2), 328-340.
[http://dx.doi.org/10.1016/j.neuron.2016.06.015] [PMID: 27477018]
[25]
Jiang, T.; Tan, L.; Zhu, X.C.; Zhang, Q.Q.; Cao, L.; Tan, M.S.; Gu, L.Z.; Wang, H.F.; Ding, Z.Z.; Zhang, Y.D.; Yu, J.T. Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer’s disease. Neuropsychopharmacology, 2014, 39(13), 2949-2962.
[http://dx.doi.org/10.1038/npp.2014.164] [PMID: 25047746]
[26]
Lee, C.Y.D.; Daggett, A.; Gu, X.; Jiang, L.L.; Langfelder, P.; Li, X.; Wang, N.; Zhao, Y.; Park, C.S.; Cooper, Y.; Ferando, I.; Mody, I.; Coppola, G.; Xu, H.; Yang, X.W. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathological phenotypes in Alzheimer’s disease models. Neuron, 2018, 97(5), 1032-1048.e5.
[http://dx.doi.org/10.1016/j.neuron.2018.02.002] [PMID: 29518357]
[27]
Zhao, Y.; Wu, X.; Li, X.; Jiang, L.L.; Gui, X.; Liu, Y.; Sun, Y.; Zhu, B.; Piña-Crespo, J.C.; Zhang, M.; Zhang, N.; Chen, X.; Bu, G.; An, Z.; Huang, T.Y.; Xu, H. TREM2 is a receptor for β-amyloid that mediates microglial function. Neuron, 2018, 97(5), 1023-1031.e7.
[http://dx.doi.org/10.1016/j.neuron.2018.01.031] [PMID: 29518356]
[28]
Kim, S.M.; Mun, B.R.; Lee, S.J.; Joh, Y.; Lee, H.Y.; Ji, K.Y.; Choi, H.R.; Lee, E.H.; Kim, E.M.; Jang, J.H.; Song, H.W.; Mook-Jung, I.; Choi, W.S.; Kang, H.S. TREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia. Sci. Rep., 2017, 7(1), 11118.
[http://dx.doi.org/10.1038/s41598-017-11634-x] [PMID: 28894284]
[29]
Lucin, K.M.; O’Brien, C.E.; Bieri, G.; Czirr, E.; Mosher, K.I.; Abbey, R.J.; Mastroeni, D.F.; Rogers, J.; Spencer, B.; Masliah, E.; Wyss-Coray, T. Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer’s disease. Neuron, 2013, 79(5), 873-886.
[http://dx.doi.org/10.1016/j.neuron.2013.06.046] [PMID: 24012002]
[30]
Ewers, M.; Biechele, G.; Suárez-Calvet, M.; Sacher, C.; Blume, T.; Morenas-Rodriguez, E.; Deming, Y.; Piccio, L.; Cruchaga, C.; Kleinberger, G.; Shaw, L.; Trojanowski, J.Q.; Herms, J.; Dichgans, M.; Brendel, M.; Haass, C.; Franzmeier, N. Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation. EMBO Mol. Med., 2020, 12(9), e12308.
[http://dx.doi.org/10.15252/emmm.202012308] [PMID: 32790063]
[31]
Zhong, L.; Xu, Y.; Zhuo, R.; Wang, T.; Wang, K.; Huang, R.; Wang, D.; Gao, Y.; Zhu, Y.; Sheng, X.; Chen, K.; Wang, N.; Zhu, L.; Can, D.; Marten, Y.; Shinohara, M.; Liu, C.C.; Du, D.; Sun, H.; Wen, L.; Xu, H.; Bu, G.; Chen, X.F. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. Nat. Commun., 2019, 10(1), 1365.
[http://dx.doi.org/10.1038/s41467-019-09118-9] [PMID: 30911003]
[32]
Fu, H.; Liu, B.; Frost, J.L.; Hong, S.; Jin, M.; Ostaszewski, B.; Shankar, G.M.; Costantino, I.M.; Carroll, M.C.; Mayadas, T.N.; Lemere, C.A. Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Aβ by microglia. Glia, 2012, 60(6), 993-1003.
[http://dx.doi.org/10.1002/glia.22331] [PMID: 22438044]
[33]
Maier, M.; Peng, Y.; Jiang, L.; Seabrook, T.J.; Carroll, M.C.; Lemere, C.A. Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J. Neurosci., 2008, 28(25), 6333-6341.
[http://dx.doi.org/10.1523/JNEUROSCI.0829-08.2008] [PMID: 18562603]
[34]
Liu, Y.; Walter, S.; Stagi, M.; Cherny, D.; Letiembre, M.; Schulz-Schaeffer, W.; Heine, H.; Penke, B.; Neumann, H.; Fassbender, K. LPS receptor (CD14): A receptor for phagocytosis of Alzheimer’s amyloid peptide. Brain, 2005, 128(8), 1778-1789.
[http://dx.doi.org/10.1093/brain/awh531] [PMID: 15857927]
[35]
Yang, C.N.; Shiao, Y.J.; Shie, F.S.; Guo, B.S.; Chen, P.H.; Cho, C.Y.; Chen, Y.J.; Huang, F.L.; Tsay, H.J. Mechanism mediating oligomeric Aβ clearance by naïve primary microglia. Neurobiol. Dis., 2011, 42(3), 221-230.
[http://dx.doi.org/10.1016/j.nbd.2011.01.005] [PMID: 21220023]
[36]
Yamanaka, M.; Ishikawa, T.; Griep, A.; Axt, D.; Kummer, M.P.; Heneka, M.T. PPARγ/RXRα-induced and CD36-mediated microglial amyloid-β phagocytosis results in cognitive improvement in amyloid precursor protein/presenilin 1 mice. J. Neurosci., 2012, 32(48), 17321-17331.
[http://dx.doi.org/10.1523/JNEUROSCI.1569-12.2012] [PMID: 23197723]
[37]
Peng, L.; Yu, Y.; Liu, J.; Li, S.; He, H.; Cheng, N.; Ye, R.D. The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide. J. Alzheimers Dis., 2014, 43(1), 227-242.
[http://dx.doi.org/10.3233/JAD-141227] [PMID: 25079809]
[38]
Griciuc, A.; Serrano-Pozo, A.; Parrado, A.R.; Lesinski, A.N.; Asselin, C.N.; Mullin, K.; Hooli, B.; Choi, S.H.; Hyman, B.T.; Tanzi, R.E. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron, 2013, 78(4), 631-643.
[http://dx.doi.org/10.1016/j.neuron.2013.04.014] [PMID: 23623698]
[39]
Pluvinage, J.V.; Haney, M.S.; Smith, B.A.H.; Sun, J.; Iram, T.; Bonanno, L.; Li, L.; Lee, D.P.; Morgens, D.W.; Yang, A.C.; Shuken, S.R.; Gate, D.; Scott, M.; Khatri, P.; Luo, J.; Bertozzi, C.R.; Bassik, M.C.; Wyss-Coray, T. CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature, 2019, 568(7751), 187-192.
[http://dx.doi.org/10.1038/s41586-019-1088-4] [PMID: 30944478]
[40]
Floden, A.M.; Combs, C.K. Microglia demonstrate age-dependent interaction with amyloid-β fibrils. J. Alzheimers Dis., 2011, 25(2), 279-293.
[http://dx.doi.org/10.3233/JAD-2011-101014] [PMID: 21403390]
[41]
Fang, Y.; Wang, J.; Yao, L.; Li, C.; Wang, J.; Liu, Y.; Tao, X.; Sun, H.; Liao, H. The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway. J. Neuroinflammation, 2018, 15(1), 210.
[http://dx.doi.org/10.1186/s12974-018-1250-1] [PMID: 30029608]
[42]
Fang, Y.; Yao, L.; Li, C.; Wang, J.; Wang, J.; Chen, S.; Zhou, X.; Liao, H. The blockage of the Nogo/NgR signal pathway in microglia alleviates the formation of Aβ plaques and tau phosphorylation in APP/PS1 transgenic mice. J. Neuroinflammation, 2016, 13(1), 56.
[http://dx.doi.org/10.1186/s12974-016-0522-x] [PMID: 26939570]
[43]
Tahara, K.; Kim, H.D.; Jin, J.J.; Maxwell, J.A.; Li, L.; Fukuchi, K. Role of toll-like receptor signalling in A uptake and clearance. Brain, 2006, 129(11), 3006-3019.
[http://dx.doi.org/10.1093/brain/awl249] [PMID: 16984903]
[44]
Liu, S.; Liu, Y.; Hao, W.; Wolf, L.; Kiliaan, A.J.; Penke, B.; Rübe, C.E.; Walter, J.; Heneka, M.T.; Hartmann, T.; Menger, M.D.; Fassbender, K. TLR2 is a primary receptor for Alzheimer’s amyloid β peptide to trigger neuroinflammatory activation. J. Immunol., 2012, 188(3), 1098-1107.
[http://dx.doi.org/10.4049/jimmunol.1101121] [PMID: 22198949]
[45]
Doi, Y.; Mizuno, T.; Maki, Y.; Jin, S.; Mizoguchi, H.; Ikeyama, M.; Doi, M.; Michikawa, M.; Takeuchi, H.; Suzumura, A. Microglia activated with the toll-like receptor 9 ligand CpG attenuate oligomeric amyloid beta neurotoxicity in in vitro and in vivo models of Alzheimer’s disease. Am. J. Pathol., 2009, 175(5), 2121-2132.
[http://dx.doi.org/10.2353/ajpath.2009.090418] [PMID: 19834064]
[46]
Lee, J.W.; Nam, H.; Kim, L.E.; Jeon, Y.; Min, H.; Ha, S.; Lee, Y.; Kim, S.Y.; Lee, S.J.; Kim, E.K.; Yu, S.W. TLR4 (toll-like receptor 4) activation suppresses autophagy through inhibition of FOXO3 and impairs phagocytic capacity of microglia. Autophagy, 2019, 15(5), 753-770.
[http://dx.doi.org/10.1080/15548627.2018.1556946] [PMID: 30523761]
[47]
Fujikura, M.; Iwahara, N.; Hisahara, S.; Kawamata, J.; Matsumura, A.; Yokokawa, K.; Saito, T.; Manabe, T.; Matsushita, T.; Suzuki, S.; Shimohama, S. CD14 and toll-like receptor 4 promote fibrillar Aβ42 uptake by microglia through a clathrin-mediated pathway. J. Alzheimers Dis., 2019, 68(1), 323-337.
[http://dx.doi.org/10.3233/JAD-180904] [PMID: 30775984]
[48]
Kim, H.J. Nucleotides released from Abeta(1)(-)(4)(2) -treated microglial cells increase cell migration and Abeta(1)(-)(4)(2) uptake through P2Y(2) receptor activation. J. Neurochem., 2012, 121, 228-238.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07700.x] [PMID: 22353164]
[49]
Li, H.; Chen, C.; Dou, Y.; Wu, H.; Liu, Y.; Lou, H.F.; Zhang, J.; Li, X.; Wang, H.; Duan, S. P2Y4 receptor-mediated pinocytosis contributes to amyloid beta-induced self-uptake by microglia. Mol. Cell. Biol., 2013, 33(21), 4282-4293.
[http://dx.doi.org/10.1128/MCB.00544-13] [PMID: 24001770]
[50]
Fu, H.; Liu, B.; Li, L.; Lemere, C.A. Microglia do not take up soluble amyloid-beta peptides, but partially degrade them by secreting insulin-degrading enzyme. Neuroscience, 2020, 443, 30-43.
[http://dx.doi.org/10.1016/j.neuroscience.2020.07.020] [PMID: 32697980]
[51]
Bergeron, N.; Phan, B.A.P.; Ding, Y.; Fong, A.; Krauss, R.M. Proprotein convertase subtilisin/kexin type 9 inhibition: A new therapeutic mechanism for reducing cardiovascular disease risk. Circulation, 2015, 132(17), 1648-1666.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.016080] [PMID: 26503748]
[52]
Fu, Y.; Hsiao, J.H.T.; Paxinos, G.; Halliday, G.M.; Kim, W.S. ABCA7 mediates phagocytic clearance of amyloid-β in the brain. J. Alzheimers Dis., 2016, 54(2), 569-584.
[http://dx.doi.org/10.3233/JAD-160456] [PMID: 27472885]
[53]
Takata, K.; Kitamura, Y.; Saeki, M.; Terada, M.; Kagitani, S.; Kitamura, R.; Fujikawa, Y.; Maelicke, A.; Tomimoto, H.; Taniguchi, T.; Shimohama, S. Galantamine-induced amyloid-beta clearance mediated via stimulation of microglial nicotinic acetylcholine receptors. J. Biol. Chem., 2010, 285(51), 40180-40191.
[http://dx.doi.org/10.1074/jbc.M110.142356] [PMID: 20947502]
[54]
Takata, K.; Amamiya, T.; Mizoguchi, H.; Kawanishi, S.; Kuroda, E.; Kitamura, R.; Ito, A.; Saito, Y.; Tawa, M.; Nagasawa, T.; Okamoto, H.; Sugino, Y.; Takegami, S.; Kitade, T.; Toda, Y.; Kem, W.R.; Kitamura, Y.; Shimohama, S.; Ashihara, E. Alpha7 nicotinic acetylcholine receptor-specific agonist DMXBA (GTS-21) attenuates Aβ accumulation through suppression of neuronal γ-secretase activity and promotion of microglial amyloid-β phagocytosis and ameliorates cognitive impairment in a mouse model of Alzheimer’s disease. Neurobiol. Aging, 2018, 62, 197-209.
[http://dx.doi.org/10.1016/j.neurobiolaging.2017.10.021] [PMID: 29175709]
[55]
Mandrekar-Colucci, S.; Karlo, J.C.; Landreth, G.E. Mechanisms underlying the rapid peroxisome proliferator-activated receptor-γ-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer’s disease. J. Neurosci., 2012, 32(30), 10117-10128.
[http://dx.doi.org/10.1523/JNEUROSCI.5268-11.2012] [PMID: 22836247]
[56]
Gaikwad, S.; Larionov, S.; Wang, Y.; Dannenberg, H.; Matozaki, T.; Monsonego, A.; Thal, D.R.; Neumann, H. Signal regulatory protein-beta1: A microglial modulator of phagocytosis in Alzheimer’s disease. Am. J. Pathol., 2009, 175(6), 2528-2539.
[http://dx.doi.org/10.2353/ajpath.2009.090147] [PMID: 19893026]
[57]
Bernstein, K.E.; Koronyo, Y.; Salumbides, B.C.; Sheyn, J.; Pelissier, L.; Lopes, D.H.J.; Shah, K.H.; Bernstein, E.A.; Fuchs, D.T.; Yu, J.J.Y.; Pham, M.; Black, K.L.; Shen, X.Z.; Fuchs, S.; Koronyo-Hamaoui, M. Angiotensin-converting enzyme overexpression in myelomonocytes prevents Alzheimer’s-like cognitive decline. J. Clin. Invest., 2014, 124(3), 1000-1012.
[http://dx.doi.org/10.1172/JCI66541] [PMID: 24487585]
[58]
Qiu, W.Q.; Walsh, D.M.; Ye, Z.; Vekrellis, K.; Zhang, J.; Podlisny, M.B.; Rosner, M.R.; Safavi, A.; Hersh, L.B.; Selkoe, D.J. Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J. Biol. Chem., 1998, 273(49), 32730-32738.
[http://dx.doi.org/10.1074/jbc.273.49.32730] [PMID: 9830016]
[59]
Gottschall, P.E.; Yu, X.; Bing, B. Increased production of gelatinase B (matrix metalloproteinase-9) and interleukin-6 by activated rat microglia in culture. J. Neurosci. Res., 1995, 42(3), 335-342.
[http://dx.doi.org/10.1002/jnr.490420307] [PMID: 8583501]
[60]
Kanemitsu, H.; Tomiyama, T.; Mori, H. Human neprilysin is capable of degrading amyloid β peptide not only in the monomeric form but also the pathological oligomeric form. Neurosci. Lett., 2003, 350(2), 113-116.
[http://dx.doi.org/10.1016/S0304-3940(03)00898-X] [PMID: 12972166]
[61]
Pawelec, P.; Ziemka-Nalecz, M.; Sypecka, J.; Zalewska, T. The impact of the CX3CL1/CX3CR1 axis in neurological disorders. Cells, 2020, 9(10), 2277.
[http://dx.doi.org/10.3390/cells9102277] [PMID: 33065974]
[62]
Hickman, S.E.; Allison, E.K.; Coleman, U.; Kingery-Gallagher, N.D.; El Khoury, J. Heterozygous CX3CR1 deficiency in microglia restores neuronal β-Amyloid clearance pathways and slows progression of Alzheimer’s like-disease in PS1-APP mice. Front. Immunol., 2019, 10, 2780.
[http://dx.doi.org/10.3389/fimmu.2019.02780] [PMID: 31849963]
[63]
Cherry, J.D.; Olschowka, J.A.; O’Banion, M.K. Arginase 1+ microglia reduce Aβ plaque deposition during IL-1β-dependent neuroinflammation. J. Neuroinflammation, 2015, 12(1), 203.
[http://dx.doi.org/10.1186/s12974-015-0411-8] [PMID: 26538310]
[64]
Ma, C.; Hunt, J.B.; Selenica, M.L.B.; Sanneh, A.; Sandusky-Beltran, L.A.; Watler, M.; Daas, R.; Kovalenko, A.; Liang, H.; Placides, D.; Cao, C.; Lin, X.; Orr, M.B.; Zhang, B.; Gensel, J.C.; Feola, D.J.; Gordon, M.N.; Morgan, D.; Bickford, P.C.; Lee, D.C. Arginase 1 insufficiency precipitates amyloid-β deposition and hastens behavioral impairment in a mouse model of amyloidosis. Front. Immunol., 2021, 11, 582998.
[http://dx.doi.org/10.3389/fimmu.2020.582998] [PMID: 33519806]
[65]
Guillot-Sestier, M.V.; Doty, K.R.; Gate, D.; Rodriguez, J., Jr; Leung, B.P.; Rezai-Zadeh, K.; Town, T. Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron, 2015, 85(3), 534-548.
[http://dx.doi.org/10.1016/j.neuron.2014.12.068] [PMID: 25619654]
[66]
Chakrabarty, P.; Li, A.; Ceballos-Diaz, C.; Eddy, J.A.; Funk, C.C.; Moore, B.; DiNunno, N.; Rosario, A.M.; Cruz, P.E.; Verbeeck, C.; Sacino, A.; Nix, S.; Janus, C.; Price, N.D.; Das, P.; Golde, T.E. IL-10 alters immunoproteostasis in APP mice, increasing plaque burden and worsening cognitive behavior. Neuron, 2015, 85(3), 519-533.
[http://dx.doi.org/10.1016/j.neuron.2014.11.020] [PMID: 25619653]
[67]
McAlpine, C.S.; Park, J.; Griciuc, A.; Kim, E.; Choi, S.H.; Iwamoto, Y.; Kiss, M.G.; Christie, K.A.; Vinegoni, C.; Poller, W.C.; Mindur, J.E.; Chan, C.T.; He, S.; Janssen, H.; Wong, L.P.; Downey, J.; Singh, S.; Anzai, A.; Kahles, F.; Jorfi, M.; Feruglio, P.F.; Sadreyev, R.I.; Weissleder, R.; Kleinstiver, B.P.; Nahrendorf, M.; Tanzi, R.E.; Swirski, F.K. Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease. Nature, 2021, 595(7869), 701-706.
[http://dx.doi.org/10.1038/s41586-021-03734-6] [PMID: 34262178]
[68]
Lian, H.; Litvinchuk, A.; Chiang, A.C.A.; Aithmitti, N.; Jankowsky, J.L.; Zheng, H. Astrocyte-microglia cross talk through complement activation modulates amyloid pathology in mouse models of Alzheimer’s Disease. J. Neurosci., 2016, 36(2), 577-589.
[http://dx.doi.org/10.1523/JNEUROSCI.2117-15.2016] [PMID: 26758846]
[69]
Mitrasinovic, O.M.; Vincent, V.A.M.; Simsek, D.; Murphy, G.M., Jr Macrophage colony stimulating factor promotes phagocytosis by murine microglia. Neurosci. Lett., 2003, 344(3), 185-188.
[http://dx.doi.org/10.1016/S0304-3940(03)00474-9] [PMID: 12812836]
[70]
Kuroda, E.; Nishimura, K.; Kawanishi, S.; Sueyoshi, M.; Ueno, F.; Toji, Y.; Abo, N.; Konishi, T.; Harada, K.; Satake, S.; Shima, C.; Toda, Y.; Kitamura, Y.; Shimohama, S.; Ashihara, E.; Takata, K. Mouse bone marrow-derived microglia-like cells secrete transforming growth factor-β1 and promote microglial Aβ phagocytosis and reduction of brain Aβ Neuroscience, 2020, 438, 217-228.
[http://dx.doi.org/10.1016/j.neuroscience.2020.05.004] [PMID: 32522344]
[71]
Casadesus, G.; Smith, M.A.; Basu, S.; Hua, J.; Capobianco, D.E.; Siedlak, S.L.; Zhu, X.; Perry, G. Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease. Mol. Neurodegener., 2007, 2(1), 2.
[http://dx.doi.org/10.1186/1750-1326-2-2] [PMID: 17241462]
[72]
Zhuang, J.; Zhang, H.; Zhou, R.; Chen, L.; Chen, J.; Shen, X. Regulation of prostaglandin F2α against β amyloid clearance and its inflammation induction through LXR/RXR heterodimer antagonism in microglia. Prostagland. Lipid Mediat., 2013, 106, 45-52.
[http://dx.doi.org/10.1016/j.prostaglandins.2013.09.002] [PMID: 24076168]
[73]
Kawabe, K.; Takano, K.; Moriyama, M.; Nakamura, Y. Microglia endocytose amyloid β through the binding of transglutaminase 2 and milk fat globule EGF factor 8 protein. Neurochem. Res., 2018, 43(1), 41-49.
[http://dx.doi.org/10.1007/s11064-017-2284-y] [PMID: 28466190]
[74]
Boza-Serrano, A.; Ruiz, R.; Sanchez-Varo, R.; García-Revilla, J.; Yang, Y.; Jimenez-Ferrer, I.; Paulus, A.; Wennström, M.; Vilalta, A.; Allendorf, D.; Davila, J.C.; Stegmayr, J.; Jiménez, S.; Roca-Ceballos, M.A.; Navarro-Garrido, V.; Swanberg, M.; Hsieh, C.L.; Real, L.M.; Englund, E.; Linse, S.; Leffler, H.; Nilsson, U.J.; Brown, G.C.; Gutierrez, A.; Vitorica, J.; Venero, J.L.; Deierborg, T. Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease. Acta Neuropathol., 2019, 138(2), 251-273.
[http://dx.doi.org/10.1007/s00401-019-02013-z] [PMID: 31006066]
[75]
Feng, W.; Zhang, Y.; Wang, Z.; Xu, H.; Wu, T.; Marshall, C.; Gao, J.; Xiao, M. Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer’s disease mouse model with suppression of glymphatic clearance. Alzheimers Res. Ther., 2020, 12(1), 125.
[http://dx.doi.org/10.1186/s13195-020-00688-1] [PMID: 33008458]
[76]
Zhang, Y.; Zhao, Y.; Zhang, J.; Yang, G. Mechanisms of NLRP3 inflammasome activation: Its role in the treatment of Alzheimer’s Disease. Neurochem. Res., 2020, 45(11), 2560-2572.
[http://dx.doi.org/10.1007/s11064-020-03121-z] [PMID: 32929691]
[77]
Dempsey, C.; Rubio Araiz, A.; Bryson, K.J.; Finucane, O.; Larkin, C.; Mills, E.L.; Robertson, A.A.B.; Cooper, M.A.; O’Neill, L.A.J.; Lynch, M.A. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice. Brain Behav. Immun., 2017, 61, 306-316.
[http://dx.doi.org/10.1016/j.bbi.2016.12.014] [PMID: 28003153]
[78]
Friker, L.L.; Scheiblich, H.; Hochheiser, I.V.; Brinkschulte, R.; Riedel, D.; Latz, E.; Geyer, M.; Heneka, M.T. β-Amyloid clustering around ASC Fibrils boosts its toxicity in microglia. Cell Rep., 2020, 30(11), 3743-3754.e6.
[http://dx.doi.org/10.1016/j.celrep.2020.02.025] [PMID: 32187546]
[79]
Wang, Y.; Leppert, A.; Tan, S.; van der Gaag, B.; Li, N.; Schultzberg, M.; Hjorth, E. Maresin 1 attenuates pro‐inflammatory activation induced by β‐amyloid and stimulates its uptake. J. Cell. Mol. Med., 2021, 25(1), 434-447.
[http://dx.doi.org/10.1111/jcmm.16098] [PMID: 33225628]
[80]
Gouwens, L.K.; Makoni, N.J.; Rogers, V.A.; Nichols, M.R. Amyloid- β42 protofibrils are internalized by microglia more extensively than monomers. Brain Res., 2016, 1648(Pt A), 485-495.
[http://dx.doi.org/10.1016/j.brainres.2016.08.016] [PMID: 27531183]
[81]
Gouwens, L.K.; Ismail, M.S.; Rogers, V.A.; Zeller, N.T.; Garrad, E.C.; Amtashar, F.S.; Makoni, N.J.; Osborn, D.C.; Nichols, M.R. Aβ42 protofibrils interact with and are trafficked through microglial-derived microvesicles. ACS Chem. Neurosci., 2018, 9(6), 1416-1425.
[http://dx.doi.org/10.1021/acschemneuro.8b00029] [PMID: 29543435]
[82]
Muraoka, S.; Jedrychowski, M.P.; Iwahara, N.; Abdullah, M.; Onos, K.D.; Keezer, K.J.; Hu, J.; Ikezu, S.; Howell, G.R.; Gygi, S.P.; Ikezu, T. Enrichment of neurodegenerative microglia signature in brain-derived extracellular vesicles isolated from Alzheimer’s Disease mouse models. J. Proteome Res., 2021, 20(3), 1733-1743.
[http://dx.doi.org/10.1021/acs.jproteome.0c00934] [PMID: 33534581]
[83]
Bolós, M.; Llorens-Martín, M.; Jurado-Arjona, J.; Hernández, F.; Rábano, A.; Avila, J. Direct evidence of internalization of Tau by microglia in vitro and in vivo. J. Alzheimers Dis., 2016, 50(1), 77-87.
[http://dx.doi.org/10.3233/JAD-150704] [PMID: 26638867]
[84]
Zilka, N.; Stozicka, Z.; Kovac, A.; Pilipcinec, E.; Bugos, O.; Novak, M. Human misfolded truncated tau protein promotes activation of microglia and leukocyte infiltration in the transgenic rat model of tauopathy. J. Neuroimmunol., 2009, 209(1-2), 16-25.
[http://dx.doi.org/10.1016/j.jneuroim.2009.01.013] [PMID: 19232747]
[85]
Litvinchuk, A.; Wan, Y.W.; Swartzlander, D.B.; Chen, F.; Cole, A.; Propson, N.E.; Wang, Q.; Zhang, B.; Liu, Z.; Zheng, H. Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in tauopathy models and Alzheimer’s Disease. Neuron, 2018, 100(6), 1337-1353.e5.
[http://dx.doi.org/10.1016/j.neuron.2018.10.031] [PMID: 30415998]
[86]
Gorlovoy, P.; Larionov, S.; Pham, T.T.H.; Neumann, H. Accumulation of tau induced in neurites by microglial proinflammatory mediators. FASEB J., 2009, 23(8), 2502-2513.
[http://dx.doi.org/10.1096/fj.08-123877] [PMID: 19289607]
[87]
Bhaskar, K.; Konerth, M.; Kokiko-Cochran, O.N.; Cardona, A.; Ransohoff, R.M.; Lamb, B.T. Regulation of tau pathology by the microglial fractalkine receptor. Neuron, 2010, 68(1), 19-31.
[http://dx.doi.org/10.1016/j.neuron.2010.08.023] [PMID: 20920788]
[88]
Maphis, N.; Xu, G.; Kokiko-Cochran, O.N.; Jiang, S.; Cardona, A.; Ransohoff, R.M.; Lamb, B.T.; Bhaskar, K. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain, 2015, 138(6), 1738-1755.
[http://dx.doi.org/10.1093/brain/awv081] [PMID: 25833819]
[89]
Bolós, M.; Llorens-Martín, M.; Perea, J.R.; Jurado-Arjona, J.; Rábano, A.; Hernández, F.; Avila, J. Absence of CX3CR1 impairs the internalization of Tau by microglia. Mol. Neurodegener., 2017, 12(1), 59.
[http://dx.doi.org/10.1186/s13024-017-0200-1] [PMID: 28810892]
[90]
Ando, K.; Brion, J.P.; Stygelbout, V.; Suain, V.; Authelet, M.; Dedecker, R.; Chanut, A.; Lacor, P.; Lavaur, J.; Sazdovitch, V.; Rogaeva, E.; Potier, M.C.; Duyckaerts, C. Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer’s brains. Acta Neuropathol., 2013, 125(6), 861-878.
[http://dx.doi.org/10.1007/s00401-013-1111-z] [PMID: 23589030]
[91]
Ando, K.; De Decker, R.; Vergara, C.; Yilmaz, Z.; Mansour, S.; Suain, V.; Sleegers, K.; de Fisenne, M.A.; Houben, S.; Potier, M.C.; Duyckaerts, C.; Watanabe, T.; Buée, L.; Leroy, K.; Brion, J.P. Picalm reduction exacerbates tau pathology in a murine tauopathy model. Acta Neuropathol., 2020, 139(4), 773-789.
[http://dx.doi.org/10.1007/s00401-020-02125-x] [PMID: 31925534]
[92]
Jiang, T.; Tan, L.; Zhu, X.C.; Zhou, J.S.; Cao, L.; Tan, M.S.; Wang, H.F.; Chen, Q.; Zhang, Y.D.; Yu, J.T. Silencing of TREM2 exacerbates tau pathology, neurodegenerative changes, and spatial learning deficits in P301S tau transgenic mice. Neurobiol. Aging, 2015, 36(12), 3176-3186.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.08.019] [PMID: 26364736]
[93]
Bemiller, S.M.; McCray, T.J.; Allan, K.; Formica, S.V.; Xu, G.; Wilson, G.; Kokiko-Cochran, O.N.; Crish, S.D.; Lasagna-Reeves, C.A.; Ransohoff, R.M.; Landreth, G.E.; Lamb, B.T. TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy. Mol. Neurodegener., 2017, 12(1), 74.
[http://dx.doi.org/10.1186/s13024-017-0216-6] [PMID: 29037207]
[94]
Leyns, C.E.G.; Ulrich, J.D.; Finn, M.B.; Stewart, F.R.; Koscal, L.J.; Remolina Serrano, J.; Robinson, G.O.; Anderson, E.; Colonna, M.; Holtzman, D.M. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc. Natl. Acad. Sci. USA, 2017, 114(43), 11524-11529.
[http://dx.doi.org/10.1073/pnas.1710311114] [PMID: 29073081]
[95]
Sayed, F.A.; Telpoukhovskaia, M.; Kodama, L.; Li, Y.; Zhou, Y.; Le, D.; Hauduc, A.; Ludwig, C.; Gao, F.; Clelland, C.; Zhan, L.; Cooper, Y.A.; Davalos, D.; Akassoglou, K.; Coppola, G.; Gan, L. Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy. Proc. Natl. Acad. Sci. USA, 2018, 115(40), 10172-10177.
[http://dx.doi.org/10.1073/pnas.1811411115] [PMID: 30232263]
[96]
Xu, Y.; Propson, N.E.; Du, S.; Xiong, W.; Zheng, H. Autophagy deficiency modulates microglial lipid homeostasis and aggravates tau pathology and spreading. Proc. Nat. Acad. Sci., 2021, 118, 8.
[http://dx.doi.org/10.1073/pnas.2023418118]
[97]
Heckmann, B.L.; Teubner, B.J.W.; Tummers, B.; Boada-Romero, E.; Harris, L.; Yang, M.; Guy, C.S.; Zakharenko, S.S.; Green, D.R. LC3-associated endocytosis facilitates β-amyloid clearance and mitigates neurodegeneration in murine Alzheimer’s Disease. Cell, 2019, 178(3), 536-551.e14.
[http://dx.doi.org/10.1016/j.cell.2019.05.056] [PMID: 31257024]
[98]
Luo, W.; Liu, W.; Hu, X.; Hanna, M.; Caravaca, A.; Paul, S.M. Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody. Sci. Rep., 2015, 5(1), 11161.
[http://dx.doi.org/10.1038/srep11161] [PMID: 26057852]
[99]
Bussian, T.J.; Aziz, A.; Meyer, C.F.; Swenson, B.L.; van Deursen, J.M.; Baker, D.J. Clearance of senescent glial cells prevents taudependent pathology and cognitive decline. Nature, 2018, 562(7728), 578-582.
[http://dx.doi.org/10.1038/s41586-018-0543-y] [PMID: 30232451]
[100]
Andersson, C.R.; Falsig, J.; Stavenhagen, J.B.; Christensen, S.; Kartberg, F.; Rosenqvist, N.; Finsen, B.; Pedersen, J.T. Antibody-mediated clearance of tau in primary mouse microglial cultures requires Fcγ-receptor binding and functional lysosomes. Sci. Rep., 2019, 9(1), 4658.
[http://dx.doi.org/10.1038/s41598-019-41105-4] [PMID: 30874605]
[101]
Lee, S.H.; Le Pichon, C.E.; Adolfsson, O.; Gafner, V.; Pihlgren, M.; Lin, H.; Solanoy, H.; Brendza, R.; Ngu, H.; Foreman, O.; Chan, R.; Ernst, J.A.; DiCara, D.; Hotzel, I.; Srinivasan, K.; Hansen, D.V.; Atwal, J.; Lu, Y.; Bumbaca, D.; Pfeifer, A.; Watts, R.J.; Muhs, A.; Scearce-Levie, K.; Ayalon, G. Antibody-mediated targeting of tau in vivo does not require effector function and microglial engagement. Cell Rep., 2016, 16(6), 1690-1700.
[http://dx.doi.org/10.1016/j.celrep.2016.06.099] [PMID: 27475227]
[102]
Das, R.; Balmik, A.A.; Chinnathambi, S. Phagocytosis of full-length Tau oligomers by Actin-remodeling of activated microglia. J. Neuroinflammation, 2020, 17(1), 10.
[http://dx.doi.org/10.1186/s12974-019-1694-y] [PMID: 31915009]
[103]
Majerova, P.; Zilkova, M.; Kazmerova, Z.; Kovac, A.; Paholikova, K.; Kovacech, B.; Zilka, N.; Novak, M. Microglia display modest phagocytic capacity for extracellular tau oligomers. J. Neuroinflammation, 2014, 11(1), 161.
[http://dx.doi.org/10.1186/s12974-014-0161-z] [PMID: 25217135]
[104]
Hopp, S.C.; Lin, Y.; Oakley, D.; Roe, A.D.; DeVos, S.L.; Hanlon, D.; Hyman, B.T. The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease. J. Neuroinflammation, 2018, 15(1), 269.
[http://dx.doi.org/10.1186/s12974-018-1309-z] [PMID: 30227881]
[105]
Asai, H.; Ikezu, S.; Tsunoda, S.; Medalla, M.; Luebke, J.; Haydar, T.; Wolozin, B.; Butovsky, O.; Kügler, S.; Ikezu, T. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci., 2015, 18(11), 1584-1593.
[http://dx.doi.org/10.1038/nn.4132] [PMID: 26436904]
[106]
Crotti, A.; Sait, H.R.; McAvoy, K.M.; Estrada, K.; Ergun, A.; Szak, S.; Marsh, G.; Jandreski, L.; Peterson, M.; Reynolds, T.L.; Dalkilic-Liddle, I.; Cameron, A.; Cahir-McFarland, E.; Ransohoff, R.M. BIN1 favors the spreading of Tau via extracellular vesicles. Sci. Rep., 2019, 9(1), 9477.
[http://dx.doi.org/10.1038/s41598-019-45676-0] [PMID: 31263146]
[107]
Ruan, Z.; Delpech, J.C.; Venkatesan Kalavai, S.; Van Enoo, A.A.; Hu, J.; Ikezu, S.; Ikezu, T. P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice. Mol. Neurodegener., 2020, 15(1), 47.
[http://dx.doi.org/10.1186/s13024-020-00396-2] [PMID: 32811520]
[108]
Audrain, M.; Haure-Mirande, J.V.; Wang, M.; Kim, S.H.; Fanutza, T.; Chakrabarty, P.; Fraser, P.; St George-Hyslop, P.H.; Golde, T.E.; Blitzer, R.D.; Schadt, E.E.; Zhang, B.; Ehrlich, M.E.; Gandy, S. Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau. Mol. Psychiatry, 2019, 24(9), 1383-1397.
[http://dx.doi.org/10.1038/s41380-018-0258-3] [PMID: 30283031]
[109]
Clayton, K.; Delpech, J.C.; Herron, S.; Iwahara, N.; Ericsson, M.; Saito, T.; Saido, T.C.; Ikezu, S.; Ikezu, T. Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model. Mol. Neurodegener., 2021, 16(1), 18.
[http://dx.doi.org/10.1186/s13024-021-00440-9] [PMID: 33752701]
[110]
Lee, S.H.; Meilandt, W.J.; Xie, L.; Gandham, V.D.; Ngu, H.; Barck, K.H.; Rezzonico, M.G.; Imperio, J.; Lalehzadeh, G.; Huntley, M.A.; Stark, K.L.; Foreman, O.; Carano, R.A.D.; Friedman, B.A.; Sheng, M.; Easton, A.; Bohlen, C.J.; Hansen, D.V. Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology. Neuron, 2021, 109(8), 1283-1301.e6.
[http://dx.doi.org/10.1016/j.neuron.2021.02.010] [PMID: 33675684]
[111]
Gratuze, M.; Chen, Y.; Parhizkar, S.; Jain, N.; Strickland, M.R.; Serrano, J.R.; Colonna, M.; Ulrich, J.D.; Holtzman, D.M. Activated microglia mitigate Aβ-associated tau seeding and spreading. J. Exp. Med., 2021, 218(8), e20210542.
[http://dx.doi.org/10.1084/jem.20210542] [PMID: 34100905]
[112]
Leyns, C.E.G.; Gratuze, M.; Narasimhan, S.; Jain, N.; Koscal, L.J.; Jiang, H.; Manis, M.; Colonna, M.; Lee, V.M.Y.; Ulrich, J.D.; Holtzman, D.M. TREM2 function impedes tau seeding in neuritic plaques. Nat. Neurosci., 2019, 22(8), 1217-1222.
[http://dx.doi.org/10.1038/s41593-019-0433-0] [PMID: 31235932]
[113]
Das, R.; Chinnathambi, S. Actin-mediated microglial chemotaxis via g-protein coupled purinergic receptor in Alzheimer’s disease. Neuroscience, 2020, 448, 325-336.
[http://dx.doi.org/10.1016/j.neuroscience.2020.09.024] [PMID: 32941933]
[114]
Heneka, M.T.; Kummer, M.P.; Stutz, A.; Delekate, A.; Schwartz, S.; Vieira-Saecker, A.; Griep, A.; Axt, D.; Remus, A.; Tzeng, T.C.; Gelpi, E.; Halle, A.; Korte, M.; Latz, E.; Golenbock, D.T. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature, 2013, 493(7434), 674-678.
[http://dx.doi.org/10.1038/nature11729] [PMID: 23254930]
[115]
Ising, C.; Venegas, C.; Zhang, S.; Scheiblich, H.; Schmidt, S.V.; Vieira-Saecker, A.; Schwartz, S.; Albasset, S.; McManus, R.M.; Tejera, D.; Griep, A.; Santarelli, F.; Brosseron, F.; Opitz, S.; Stunden, J.; Merten, M.; Kayed, R.; Golenbock, D.T.; Blum, D.; Latz, E.; Buée, L.; Heneka, M.T. NLRP3 inflammasome activation drives tau pathology. Nature, 2019, 575(7784), 669-673.
[http://dx.doi.org/10.1038/s41586-019-1769-z] [PMID: 31748742]
[116]
Kim, J.; Lee, Y.; Lee, S.; Kim, K.; Song, M.; Lee, J. Mesenchymal stem cell therapy and Alzheimer’s Disease: Current status and future perspectives. J. Alzheimers Dis., 2020, 77(1), 1-14.
[http://dx.doi.org/10.3233/JAD-200219] [PMID: 32741816]
[117]
Bernardo, M.E.; Locatelli, F.; Fibbe, W.E. Mesenchymal stromal cells. Ann. N. Y. Acad. Sci., 2009, 1176(1), 101-117.
[http://dx.doi.org/10.1111/j.1749-6632.2009.04607.x] [PMID: 19796238]
[118]
Hernández, A.E.; García, E. Mesenchymal stem cell therapy for Alzheimer’s Disease. Stem Cells Int., 2021, 2021, 7834421.
[http://dx.doi.org/10.1155/2021/7834421] [PMID: 34512767]
[119]
Lee, J.K.; Jin, H.K.; Bae, J. Bone marrow-derived mesenchymal stem cells reduce brain amyloid-β deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neurosci. Lett., 2009, 450(2), 136-141.
[http://dx.doi.org/10.1016/j.neulet.2008.11.059] [PMID: 19084047]
[120]
Lee, J.K.; Schuchman, E.H.; Jin, H.K.; Bae, J.S. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid β ameliorates Alzheimer’s disease in mice by recruiting bone marrow-induced microglia immune responses. Stem Cells, 2012, 30(7), 1544-1555.
[http://dx.doi.org/10.1002/stem.1125] [PMID: 22570192]
[121]
Kuroda, E.; Takata, K.; Nishimura, K.; Oka, H.; Sueyoshi, M.; Aitani, M.; Kouda, A.; Satake, S.; Shima, C.; Toda, Y.; Nakata, S.; Kitamura, Y.; Ashihara, E. Peripheral blood-derived microglia-like cells decrease amyloid-β burden and ameliorate cognitive impairment in a mouse model of Alzheimer’s Disease. J. Alzheimers Dis., 2020, 73(1), 413-429.
[http://dx.doi.org/10.3233/JAD-190974] [PMID: 31796681]
[122]
Ostrowitzki, S.; Deptula, D.; Thurfjell, L.; Barkhof, F.; Bohrmann, B.; Brooks, D.J.; Klunk, W.E.; Ashford, E.; Yoo, K.; Xu, Z.X.; Loetscher, H.; Santarelli, L. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch. Neurol., 2012, 69(2), 198-207.
[http://dx.doi.org/10.1001/archneurol.2011.1538] [PMID: 21987394]
[123]
Sevigny, J.; Chiao, P.; Bussière, T.; Weinreb, P.H.; Williams, L.; Maier, M.; Dunstan, R.; Salloway, S.; Chen, T.; Ling, Y.; O’Gorman, J.; Qian, F.; Arastu, M.; Li, M.; Chollate, S.; Brennan, M.S.; Quintero-Monzon, O.; Scannevin, R.H.; Arnold, H.M.; Engber, T.; Rhodes, K.; Ferrero, J.; Hang, Y.; Mikulskis, A.; Grimm, J.; Hock, C.; Nitsch, R.M.; Sandrock, A. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature, 2016, 537(7618), 50-56.
[http://dx.doi.org/10.1038/nature19323] [PMID: 27582220]
[124]
Lannfelt, L.; Möller, C.; Basun, H.; Osswald, G.; Sehlin, D.; Satlin, A.; Logovinsky, V.; Gellerfors, P. Perspectives on future Alzheimer therapies: amyloid-β protofibrils-a new target for immunotherapy with BAN2401 in Alzheimer’s disease. Alzheimers Res. Ther., 2014, 6(2), 16.
[http://dx.doi.org/10.1186/alzrt246] [PMID: 25031633]
[125]
Pradier, L.; Blanchard-Brégeon, V.; Bohme, A.; Debeir, T.; Menager, J.; Benoit, P.; Barneoud, P.; Taupin, V.; Bertrand, P.; Dugay, P.; Cameron, B.; Shi, Y.; Naimi, S.; Duchesne, M.; Gagnaire, M.; Weeden, T.; Travaline, T.; Reczek, D.; Khiroug, L.; Slaoui, M.; Brunel, P.; Fukuyama, H.; Ravetch, J.; Canton, T.; Cohen, C. SAR228810: an antibody for protofibrillar amyloid β peptide designed to reduce the risk of amyloid-related imaging abnormalities (ARIA). Alzheimers Res. Ther., 2018, 10(1), 117.
[http://dx.doi.org/10.1186/s13195-018-0447-y] [PMID: 30486882]
[126]
Frost, C.V.; Zacharias, M. From monomer to fibril: Abeta‐amyloid binding to Aducanumab antibody studied by molecular dynamics simulation. Proteins, 2020, 88(12), 1592-1606.
[http://dx.doi.org/10.1002/prot.25978] [PMID: 32666627]
[127]
Plotkin, S.S.; Cashman, N.R. Passive immunotherapies targeting Aβ and tau in Alzheimer’s disease. Neurobiol. Dis., 2020, 144, 105010.
[http://dx.doi.org/10.1016/j.nbd.2020.105010] [PMID: 32682954]
[128]
Xiang, X.; Werner, G.; Bohrmann, B.; Liesz, A.; Mazaheri, F.; Capell, A.; Feederle, R.; Knuesel, I.; Kleinberger, G.; Haass, C. TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. EMBO Mol. Med., 2016, 8(9), 992-1004.
[http://dx.doi.org/10.15252/emmm.201606370] [PMID: 27402340]
[129]
Ayalon, G.; Lee, S.H.; Adolfsson, O.; Foo-Atkins, C.; Atwal, J.K.; Blendstrup, M.; Booler, H.; Bravo, J.; Brendza, R.; Brunstein, F.; Chan, R.; Chandra, P.; Couch, J.A.; Datwani, A.; Demeule, B.; DiCara, D.; Erickson, R.; Ernst, J.A.; Foreman, O.; He, D.; Hötzel, I.; Keeley, M.; Kwok, M.C.M.; Lafrance-Vanasse, J.; Lin, H.; Lu, Y.; Luk, W.; Manser, P.; Muhs, A.; Ngu, H.; Pfeifer, A.; Pihlgren, M.; Rao, G.K.; Scearce-Levie, K.; Schauer, S.P.; Smith, W.B.; Solanoy, H.; Teng, E.; Wildsmith, K.R.; Bumbaca Yadav, D.; Ying, Y.; Fuji, R.N.; Kerchner, G.A. Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer’s disease. Sci. Transl. Med., 2021, 13(593), eabb2639.
[http://dx.doi.org/10.1126/scitranslmed.abb2639] [PMID: 33980574]
[130]
Sopko, R.; Golonzhka, O.; Arndt, J.; Quan, C.; Czerkowicz, J.; Cameron, A.; Smith, B.; Murugesan, Y.; Gibbons, G.; Kim, S.J.; Trojanowski, J.Q.; Lee, V.M.Y.; Brunden, K.R.; Graham, D.L.; Weinreb, P.H.; Hering, H. Characterization of tau binding by gosuranemab. Neurobiol. Dis., 2020, 146, 105120.
[http://dx.doi.org/10.1016/j.nbd.2020.105120] [PMID: 32991997]
[131]
Novak, P.; Zilka, N.; Zilkova, M.; Kovacech, B.; Skrabana, R.; Ondrus, M.; Fialova, L.; Kontsekova, E.; Otto, M.; Novak, M. AADvac1, an active immunotherapy for Alzheimer’s Disease and non-Alzheimer Tauopathies: An overview of preclinical and clinical development. J. Prev. Alzheimers Dis., 2019, 6(1), 63-69.
[PMID: 30569088]
[132]
Walsh, S.; Merrick, R.; Milne, R.; Brayne, C. Aducanumab for Alzheimer’s disease? BMJ, 2021, 374, n1682.
[http://dx.doi.org/10.1136/bmj.n1682] [PMID: 34226181]
[133]
Salloway, S.; Farlow, M.; McDade, E.; Clifford, D.B.; Wang, G.; Llibre-Guerra, J.J.; Hitchcock, J.M.; Mills, S.L.; Santacruz, A.M.; Aschenbrenner, A.J.; Hassenstab, J.; Benzinger, T.L.S.; Gordon, B.A.; Fagan, A.M.; Coalier, K.A.; Cruchaga, C.; Goate, A.A.; Perrin, R.J.; Xiong, C.; Li, Y.; Morris, J.C.; Snider, B.J.; Mummery, C.; Surti, G.M.; Hannequin, D.; Wallon, D.; Berman, S.B.; Lah, J.J.; Jimenez-Velazquez, I.Z.; Roberson, E.D.; van Dyck, C.H.; Honig, L.S.; Sánchez-Valle, R.; Brooks, W.S.; Gauthier, S.; Galasko, D.R.; Masters, C.L.; Brosch, J.R.; Hsiung, G.Y.R.; Jayadev, S.; Formaglio, M.; Masellis, M.; Clarnette, R.; Pariente, J.; Dubois, B.; Pasquier, F.; Jack, C.R., Jr; Koeppe, R.; Snyder, P.J.; Aisen, P.S.; Thomas, R.G.; Berry, S.M.; Wendelberger, B.A.; Andersen, S.W.; Holdridge, K.C.; Mintun, M.A.; Yaari, R.; Sims, J.R.; Baudler, M.; Delmar, P.; Doody, R.S.; Fontoura, P.; Giacobino, C.; Kerchner, G.A.; Bateman, R.J.; Formaglio, M.; Mills, S.L.; Pariente, J.; van Dyck, C.H. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat. Med., 2021, 27(7), 1187-1196.
[http://dx.doi.org/10.1038/s41591-021-01369-8] [PMID: 34155411]
[134]
Teng, E.; Manser, P.T.; Pickthorn, K.; Brunstein, F.; Blendstrup, M.; Sanabria Bohorquez, S.; Wildsmith, K.R.; Toth, B.; Dolton, M.; Ramakrishnan, V.; Bobbala, A.; Sikkes, S.A.M.; Ward, M.; Fuji, R.N.; Kerchner, G.A.; Farnbach, P.; Kyndt, C.; O’Brien, T.; Yassi, N.; Schwartz, R.; Lieten, S.; Vandenberghe, R.; Vanhee, F.; Bergeron, R.; Black, S.; Cohen, S.; Frank, A.; Nisker, W.; Tartaglia, M.C.; Justesen, A.; Alexandersen, P.; Nielsen, S.; Areovimata, A.; Anthony, P.; Belliard, S.; Blanc, F.; Ceccaldi, M.; Dubois, B.; Krolak-Salmon, P.; Mollion, H.; Pasquier, F.; Grimmer, T.; Kottke-Arbeiter, M.E.; Laske, C.; Peters, O.; Polivka, D.; von Arnim, C.; Bruno, G.; De Lena, C.; Cassetta, E.; Centonze, D.; Logroscino, G.; Dautzenberg, P.; Rutgers, S.; Prins, N.; Czarnecki, M.; Dobryniewski, J.; Ilkowski, J.; Klodowska, G.; Krygowska-Wajs, A.; Kucharski, R.; Mickielewicz, A.; Ratajczak, M.; Zboch, M.; Zielinski, T.; Abizanda Soler, P.; Agüera Morales, E.; Baquero Toledo, M.; Blesa González, R.; Boada Rovira, M.; Del Olmo Rodriguez, A.; Krupinski, J.; Linazasoro Cristobal, G.; López Arrieta, J.; Riverol Fernandez, M.; Sanchez Del Valle Diaz, R.; Viñuela Fernandez, F.; Jonsson, M.; Östlund, H.; MacSweeney, J.E.; Mummery, C.; Agronin, M.; Ala, T.; Bond, W.; Schaerf, F.; Brody, M.; Edwards, K.; Forchetti, C.; Sood, A.; Geldmacher, D.; Goldstein, M.; Goodman, I.; Hart, D.; Honig, L.; Justiz, W.; Levey, A.; Losk, S.; Marshall, G.; Martinez, W.; McAllister, P.; McElveen, W.A.; Maldonado-Robles, O.; Murphy, C.; Nair, M.; Nair, A.; Omidvar, O.; Oskooilar, N.; Porsteinsson, A.; Rosenbloom, M.; Russell, D.; Sajjadi, S.A.; Pierce, A.; Salloway, S.; Sha, S.; Shah, R.; Sharma, S.; Smith, W.; Stein, L.; Stoukides, J.; Thein, S.; Turner, R.; Watson, D.; Weisman, D. Safety and efficacy of Semorinemab in individuals with prodromal to mild Alzheimer Disease. JAMA Neurol., 2022, 79(8), 758-767.
[http://dx.doi.org/10.1001/jamaneurol.2022.1375] [PMID: 35696185]
[135]
The, L. Lecanemab for Alzheimer’s disease: Tempering hype and hope. Lancet, 2022, 400(10367), 1899.
[http://dx.doi.org/10.1016/S0140-6736(22)02480-1] [PMID: 36463893]
[136]
Söderberg, L.; Johannesson, M.; Nygren, P.; Laudon, H.; Eriksson, F.; Osswald, G.; Möller, C.; Lannfelt, L. Lecanemab, Aducanumab, and Gantenerumab — Binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for Alzheimer’s Disease. Neurotherapeutics, 2022. [Epub ahead print].
[http://dx.doi.org/10.1007/s13311-022-01308-6] [PMID: 36253511]
[137]
Pan, R.Y.; Ma, J.; Kong, X.X.; Wang, X.F.; Li, S.S.; Qi, X.L.; Yan, Y.H.; Cheng, J.; Liu, Q.; Jin, W.; Tan, C.H.; Yuan, Z. Sodium rutin ameliorates Alzheimer’s disease–like pathology by enhancing microglial amyloid-β clearance. Sci. Adv., 2019, 5(2), eaau6328.
[http://dx.doi.org/10.1126/sciadv.aau6328] [PMID: 30820451]
[138]
Park, M.H.; Lee, M.; Nam, G.; Kim, M.; Kang, J.; Choi, B.J.; Jeong, M.S.; Park, K.H.; Han, W.H.; Tak, E.; Kim, M.S.; Lee, J.; Lin, Y.; Lee, Y.H.; Song, I.S.; Choi, M.K.; Lee, J.Y.; Jin, H.K.; Bae, J.; Lim, M.H. N, N ′-Diacetyl- p -phenylenediamine restores microglial phagocytosis and improves cognitive defects in Alzheimer’s disease transgenic mice. Proc. Natl. Acad. Sci. USA, 2019, 116(47), 23426-23436.
[http://dx.doi.org/10.1073/pnas.1916318116] [PMID: 31685616]
[139]
Zhang, C.; Griciuc, A.; Hudry, E.; Wan, Y.; Quinti, L.; Ward, J.; Forte, A.M.; Shen, X.; Ran, C.; Elmaleh, D.R.; Tanzi, R.E. Cromolyn reduces levels of the Alzheimer’s disease-associated amyloid β-protein by promoting microglial phagocytosis. Sci. Rep., 2018, 8(1), 1144.
[http://dx.doi.org/10.1038/s41598-018-19641-2] [PMID: 29348604]
[140]
Connor, S.M.; Rashid, M.; Ryan, K.J.; Patel, K.; Boyd, J.D.; Smith, J.; Elyaman, W.; Bennett, D.A.; Bradshaw, E.M. GW5074 increases microglial phagocytic activities: Potential therapeutic direction for Alzheimer’s disease. Front. Cell. Neurosci., 2022, 16, 894601.
[http://dx.doi.org/10.3389/fncel.2022.894601] [PMID: 35677758]
[141]
Lv, J.; Wang, W.; Zhu, X.; Xu, X.; Yan, Q.; Lu, J.; Shi, X.; Wang, Z.; Zhou, J.; Huang, X.; Wang, J.; Duan, W.; Shen, X. DW14006 as a direct AMPKα1 activator improves pathology of AD model mice by regulating microglial phagocytosis and neuroinflammation. Brain Behav. Immun., 2020, 90, 55-69.
[http://dx.doi.org/10.1016/j.bbi.2020.07.041] [PMID: 32739363]
[142]
Wang, S.; Mustafa, M.; Yuede, C.M.; Salazar, S.V.; Kong, P.; Long, H.; Ward, M.; Siddiqui, O.; Paul, R.; Gilfillan, S.; Ibrahim, A.; Rhinn, H.; Tassi, I.; Rosenthal, A.; Schwabe, T.; Colonna, M. Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model. J. Exp. Med., 2020, 217(9), e20200785.
[http://dx.doi.org/10.1084/jem.20200785] [PMID: 32579671]
[143]
Ulrich, J.D.; Finn, M.B.; Wang, Y.; Shen, A.; Mahan, T.E.; Jiang, H.; Stewart, F.R.; Piccio, L.; Colonna, M.; Holtzman, D.M. Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2. Mol. Neurodegener., 2014, 9(1), 20.
[http://dx.doi.org/10.1186/1750-1326-9-20] [PMID: 24893973]

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