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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Re-Balancing of Inflammation and Aβ Immunity as a Therapeutic for Alzheimers Disease-View from the Bedside

Author(s): Milan Fiala

Volume 9, Issue 2, 2010

Page: [192 - 196] Pages: 5

DOI: 10.2174/187152710791012044

Price: $65


Morbidities of aging and Alzheimers disease (AD) have been related to defective functions of both T cells and macrophages leading to brain amyloidosis and inflammation. In AD patients, “inflammaging” may be associated with an increase of incompetent memory T cells and inflammatory cytokines produced by macrophages, whereas defective clearance of amyloid-β 1-42 (Aβ) may be related to defective transcription of immune genes necessary for Aβ phagocytosis, β-1,4-mannosyl-glycoprotein 4-β-Nacetylglucosaminyltransferase and Toll-like receptors. However, AD shows considerable heterogeneity of disease manifestations and mechanisms. The approaches to re-balancing Aβ immunity and inflammation are being pursued in transgenic animal models and peripheral blood mononuclear cells of patients. The regulatory signaling pathways of microglial phagocytosis and inflammation involving co-receptors and transforming growth factor-β have been considerably clarified in animal studies. Natural immunostimulating therapies using vitamin D3 and curcuminoids have been developed in macrophages of AD patients. AD patients possess two types of macrophages: a majority has “Type I”, which are improved by curcuminoids and vitamin D3; whereas a minority has “Type II” responding positively to vitamin D3 but not to curcuminoids. Other nutritional substances, such as plant polyphenols and omega-3 fatty acids, may inhibit inflammation and stimulate immunity. More invasive immune approaches involve Aβ vaccine and cytokine antagonists. Increased inflammation may represent the “first hit”, and defective transcription of immune genes the “second hit” in the pathogenesis of AD.

Keywords: Alzheimer's Disease, immune Aβ hypothesis, nutrition, vitamin 1β, 25 (OH)2 vitamin D3 eicosapentaenoic acid, curcuminoids, regulatory T cells

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