title: Role of complement systems in IVIG mediated attenuation of cognitive deterioration in Alzheimer's disease.
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.
authors.forename: Bing
authors.initials: B
authors.lastname: Gong
authors.forename: Samara
authors.initials: S
authors.lastname: Levine
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
authors.affiliation: Mount Sinai School of Medicine, Department of Neurology, 1468 Madison Avenue, New York, NY 10029, USA. giulio.pasinetti@mssm.edu.
authors.forename: Giulio M
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D003072:Cognition Disorders / Q000503:physiopathology / Q000628:therapy*; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D018091:Receptors, AMPA; D003165:Complement System Proteins