Neuroimmune mechanisms in Alzheimer disease pathogenesis.
Lesions in Alzheimer disease are characterized by the assembly of a variety of cells and proteins associated with the immune system. Activated microglia express high levels of major histocompatibility complex glycoproteins and receptors for complement. Small numbers of T lymphocytes infiltrate tissue. Proteins of the classical complement pathway are closely connected with beta-amyloid deposits. beta-Amyloid protein binds C1q in vitro and activates the pathway. The membrane attack complex of complement, as well as proteins that defend against that complex, colocalize with dystrophic neurites. These data imply that an autodestructive process is occurring in Alzheimer disease, that overactive microglia might be responsible, and that antiinflammatory drugs might be an effective form of therapy.
McGeer
P L
PL
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.
Rogers
J
J
McGeer
E G
EG
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000276:immunology; D009410:Nerve Degeneration; D013601:T-Lymphocytes / Q000276:immunology
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015938:Complement Membrane Attack Complex