Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down Syndrome

Neurobiol Dis. 2001 Apr;8(2):252-65. doi: 10.1006/nbdi.2000.0380.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Aging / metabolism
  • Aging / pathology
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism*
  • Benzothiazoles
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • Complement C1q / immunology
  • Complement C1q / metabolism*
  • Down Syndrome / immunology*
  • Down Syndrome / metabolism
  • Down Syndrome / pathology
  • Encephalitis / immunology
  • Encephalitis / metabolism
  • Encephalitis / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Microglia / immunology
  • Microglia / metabolism
  • Microglia / pathology
  • Middle Aged
  • Neurofibrillary Tangles / immunology
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology
  • Neurons / immunology*
  • Neurons / metabolism
  • Neurons / pathology
  • Plaque, Amyloid / immunology
  • Plaque, Amyloid / metabolism
  • Plaque, Amyloid / pathology
  • Thiazoles / metabolism

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Thiazoles
  • thioflavin T
  • Complement C1q