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- Title
Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype.
- Authors
Tanskanen, M.; Lindsberg, P. J.; Tienari, P. J.; Polvikoski, T.; Sulkava, R.; Verkkoniemi, A.; Rastas, S.; Paetau, A.; Kiuru-Enari, S.
- Abstract
There is growing evidence that in Alzheimer's disease (AD) amyloid β-protein (Aβ) triggers a chronic inflammatory reaction in cerebral amyloid plaques, including complement proteins. Aβ 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 Aβ 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 ℇ4 ( P = 0.0005) and overrepresentation of ℇ4 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 ℇ4+ ( P = 0.02) and ℇ4 – ( P = 0.06) subjects. Our study shows that complement proteins are deposited in the affected vessels in Aβ– associated CAA. They may solely represent the cerebral Aβ– burden associated to inflammatory stimuli, or signal a contribution in the clearance of cerebral Aβ, thereby contributing to the events associated with evolution of clinical dementia. Our results demonstrate a strong association between CAA and ApoE ℇ4 as well as dementia and suggest that the contribution of CAA to dementia is largely independent of ApoE ℇ4.
- Subjects
ALZHEIMER'S disease; APOLIPOPROTEIN E; PROTEINS; IMMUNOHISTOCHEMISTRY; PROTEOMICS; GENETICS
- Publication
Neuropathology & Applied Neurobiology, 2005, Vol 31, Issue 6, p589
- ISSN
0305-1846
- Publication type
Article
- DOI
10.1111/j.1365-2990.2005.00652.x