Histological and Direct Evidence for the Role of Complement in the Neuroinflammation of AD

Author(s): Robert Veerhuis.

Journal Name: Current Alzheimer Research

Volume 8 , Issue 1 , 2011

">

Abstract:

In Alzheimerss disease (AD) a disturbed balance between synthesis and removal of Aβ leads to the formation of Aβ deposits and a reaction of the innate immune system. Little evidence exists for a contribution of the adaptive immune response in AD, as no signs of influx of blood borne cells or presence of immunoglobulins in Aβ deposits are apparent. Factors of the complement (C) system and pentraxins act as pattern recognition molecules and mediate uptake of Aβ by glial cells expressing C-receptors (Crec). These interactions may, however, also lead to synthesis and secretion of reactive oxygen species (ROS), cytokines, chemokines and other potentially neurotoxic agents by the glial cells. Virtually all complement factors are produced in brain, and the expression is increased in AD affected brain areas. In AD brain areas with amyloid deposits especially classical pathway C activation products are readily observed. Also C regulatory proteins (Creg) and Crec can be found in the brain parenchyma and are upregulated, especially under acute inflammatory conditions, such as meningitis. However, under chronic low-grade inflammatory conditions, such as in AD, Creg and to some extent Crec expression may remain at a low level, thereby allowing C activation to proceed, leading to sustained activation of glial cells and neurodegenerative changes. In this review evidence from immunohistochemical, in vitro and animal studies pointing to a role for C activation is discussed, with special focus on the disturbed balance between C activators and Cregs in AD.

Keywords: Complement, complement receptors, Alzheimer's disease, amyloid, microglia, neuroinflammation, Amyloid plaques, Vascular amyloid, Cerebral amyloid angiopathy, Age related macula degeneration (AMD), Complement regulatory proteins (Creg), C1q, C1-Inhibitor, Factor H, Clusterin

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 8
ISSUE: 1
Year: 2011
Page: [34 - 58]
Pages: 25
DOI: 10.2174/156720511794604589

Article Metrics

PDF: 43