Elsevier

Neurobiology of Disease

Volume 8, Issue 2, April 2001, Pages 252-265
Neurobiology of Disease

Regular Article
Complement Association with Neurons and β-Amyloid Deposition in the Brains of Aged Individuals with Down Syndrome

https://doi.org/10.1006/nbdi.2000.0380Get rights and content

Abstract

To study the link between β-amyloid (Aβ) and neuroinflammation, we examined the levels of complement as a function of age and extent of Aβ 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 Aβ plaques in DS brain and increased with more extensive age-dependent Aβ deposition. In contrast, little or no C1q labeling was associated with diffuse or thioflavine-S negative Aβ 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 Aβ-mediated inflammatory factors contributing to the rapid accumulation of neuropathology in DS brain.

References (65)

  • E. Gowing et al.

    Chemical characterization of Aβ17-42 peptide, a component of diffuse amyloid deposits of Alzheimer's disease

    J. Biol. Chem.

    (1994)
  • T. Iwatsubo et al.

    Visualization of AB42(43) and AB40 in senile plaques with end-specific AB monoclonals: Evidence that an initially deposited species is AB42(43)

    Neuron

    (1994)
  • S.A. Johnson et al.

    Complement mRNA in the mammalian brain: Responses to Alzheimer's disease and experimental brain lesioning

    Neurobiol. Aging

    (1992)
  • C.A. Lemere et al.

    Sequence of deposition of heterogeneous amyloid beta-peptides and APOE in Down Syndrome: Implications for initial events in amyloid plaque formation

    Neurobiol. Dis.

    (1996)
  • J.B. Leverenz et al.

    Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: A regional quantitative analysis

    Exp. Neurol.

    (1998)
  • D.M.A. Mann

    The pathological association between Down syndrome and Alzheimer disease

    Mech. Ageing Dev.

    (1988)
  • D.M.A. Mann et al.

    The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome

    J. Neurol. Sci.

    (1989)
  • P.L. McGeer et al.

    The inflammatory response system of brain: Implications for therapy of Alzheimer and other neurodegenerative diseases

    Brain Res. Rev.

    (1995)
  • B.P. Morgan et al.

    Expression of complement in the brain: Role in health and disease

    Immunol. Today

    (1996)
  • G.M. Pasinetti

    Inflammatory mechanisms in neurodegeneration and Alzheimer's disease: The role of the complement system

    Neurobiol. Aging

    (1996)
  • H. Potter

    The involvement of astrocytes and an acute phase response in the amyloid deposition of Alzheimer's disease

    Prog. Brain Res.

    (1992)
  • T.C. Saido et al.

    Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3 (pE), in senile plaques

    Neuron

    (1995)
  • D.J. Selkoe

    Amyloid beta-protein and the genetics of Alzheimer's disease

    J. Biol. Chem.

    (1996)
  • Y. Shen et al.

    Neuronal expression mRNAs for complement proteins of the classical pathway in Alzheimer brain

    Brain Res.

    (1997)
  • S.K. Singhrao et al.

    Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease

    Exp. Neurol.

    (1999)
  • S.E. Stoltzner et al.

    Temporal accrual of complement proteins in amyloid plaques in Down's syndrome with Alzheimer's disease

    Am. J. Pathol.

    (2000)
  • K. Terai et al.

    Neurons express proteins of the classical complement pathway in Alzheimer disease

    Brain Res.

    (1997)
  • S. Webster et al.

    Multivalent binding of complement protein C1q to the amyloid β-peptide promotes the nucleation phase of Aβ aggregation

    Biochem. Biophys. Res. Commun.

    (1995)
  • S.D. Webster et al.

    Complement component C1q modulates the phagocytosis of Aβ by microglia

    Exp. Neurol.

    (2000)
  • H.M. Wisniewski et al.

    The role of perivascular and microglial cells in fibrillogenesis of beta-amyloid and PrP protein in Alzheimer's disease and scrapie

    Res. Immunol.

    (1992)
  • B.A. Yankner

    Mechanisms of neuronal degeneration in Alzheimer's disease

    Neuron

    (1996)
  • S.R. Barnum

    Complement biosynthesis in the central nervous system

    Crit. Rev. Oral. Biol. Med.

    (1995)
  • Cited by (0)

    View full text