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Cerebral amyloid angiopathy in a 95+cohort: complement activation and apolipoprotein E (ApoE) genotype

Lookup NU author(s): Dr Tuomo Polvikoski


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There is growing evidence that in Alzheimer's disease (AD) amyloid beta-protein (A beta) triggers a chronic inflammatory reaction in cerebral amyloid plaques, including complement proteins. A beta also accumulates cerebrovascularly in age- and AD-associated cerebral amyloid angiopathy (CAA). We investigated complement proteins in CAA in a population-based series using histological and immunohistochemical staining methods. The 74 subjects, aged 95 years or more, had undergone clinical neurological examination and apolipoprotein E (ApoE) genotyping. The brains had been studied for AD post-mortem, allowing us to relate the histopathological findings to clinical and genetic conditions. CAA with congophilic amyloid was found in 36/74 individuals (48.6%). The vascular amyloid deposits immunoreacted with antibodies to A beta and complements 3d (C3d) and 9 (C9). The positivity in complement stains increased with growing severity of CAA (P = 0.001). The presence of CAA associated with ApoE epsilon 4 (P = 0.0005) and overrepresentation of epsilon 4 among those with moderate or severe vs. mild CAA (P = 0.03) was demonstrated. The presence of CAA associated with dementia (P = 0.01), which was contributed by both epsilon 4+ (P = 0.02) and epsilon 4 - (P = 0.06) subjects. Our study shows that complement proteins are deposited in the affected vessels in A beta- associated CAA. They may solely represent the cerebral A beta- burden associated to inflammatory stimuli, or signal a contribution in the clearance of cerebral A beta, thereby contributing to the events associated with evolution of clinical dementia. Our results demonstrate a strong association between CAA and ApoE epsilon 4 as well as dementia and suggest that the contribution of CAA to dementia is largely independent of ApoE epsilon 4.

Publication metadata

Author(s): Tanskanen M, Lindsberg PJ, Tienari PJ, Polvikoski T, Sulkava R, Verkkoniemi A, Rastas S, Paetau A, Kiuru-Enari S

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2005

Volume: 31

Issue: 6

Pages: 589-599

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley


DOI: 10.1111/j.1365-2990.2005.00652.x


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