Title:Role of Complement Systems in IVIG Mediated Attenuation of Cognitive Deterioration in Alzheimer's Disease
Volume: 11
Issue: 7
Author(s): Bing Gong, Samara Levine, Scott R. Barnum and Giulio M. Pasinetti
Affiliation:
Keywords:
Alzheimer's disease, cognitive function, complement component, immunotherapy, IVIG, synaptic plasticity.
Abstract: Human intravenous immunoglobulin (IVIG) has been indicated as a potential therapy for autoimmune neurological
disorders, as well as in many neurodegenerative diseases, with various underlying therapeutic mechanisms such as
regulation of T-cell trafficking, cytokines, Fc receptor blocking, and interruption of complement activation cascade. In
Alzheimer’s disease (AD), IVIG presents naturally occurring antibodies against amyloid-beta (Aβ) aggregation, thus IVIG
immunotherapy may increase the clearance of Aβ and protect brain function. Recently, we and others reported that besides
Aβ clearance, IVIG specifically regulates the levels of complement-derived anaphylatoxins, such as C5a and C3,
which play an important role in the regulation of AMPA and NMDA receptor expression in the brain and further upregulate
the AMPA-PKA-CREB signaling pathway and synaptic function in AD mouse models. Since down-regulation of
complement components has been linked with deficits of cognitive function in age-related dementia following the decline
of innate immunity during aging, the IVIG immunotherapy could be an attractive novel AD therapeutic through its local
regulation of C3, C5a component levels in brain.
