Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down Syndrome.
To study the link between beta-amyloid (Abeta) and neuroinflammation, we examined the levels of complement as a function of age and extent of Abeta deposition in Down Syndrome (DS) brain. C1q, the first component of the complement cascade, was visualized using immunohistochemistry in the frontal, entorhinal cortex, and hippocampus of 12 DS ranging from 31 to 69 years of age. C1q was consistently associated with thioflavine-S positive Abeta plaques in DS brain and increased with more extensive age-dependent Abeta deposition. In contrast, little or no C1q labeling was associated with diffuse or thioflavine-S negative Abeta deposits. Neurons in the hippocampus and entorhinal cortex, but less frequently in frontal cortex, were C1q positive in DS cases with sufficient neuropathology to have a diagnosis of Alzheimer's disease. C1q-positive neurons were associated with activated microglia. These results provide evidence for Abeta-mediated inflammatory factors contributing to the rapid accumulation of neuropathology in DS brain.
Head
E
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Institute for Brain Aging and Dementia, University of California, Irvine, California 92697-4540, USA.
Azizeh
B Y
BY
Lott
I T
IT
Tenner
A J
AJ
Cotman
C W
CW
Cribbs
D H
DH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D052160:Benzothiazoles; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D004314:Down Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D013844:Thiazoles; C009462:thioflavin T; D015922:Complement C1q