Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex.

Abstract:

:Studies in vitro have suggested that acetylcholinesterase (AChE) may interact with beta-amyloid to promote deposition of amyloid plaques in the brain of patients with Alzheimer's disease. To test that hypothesis in vivo, we crossed Tg2576 mice, which express human amyloid precursor protein and develop plaques at 9 months, with transgenic mice expressing human AChE. The resulting F1 hybrids (FVB/N x [C57B6 x SJL/J]) expressed both transgenes in brain. By 6 months of age, their cerebral cortex showed authentic plaques that stained both by thioflavin S and by beta-amyloid 1-40 and 1-42 immunohistochemistry. The plaques also stained positively for other components including Cd11b, GFAP, and AChE. Plaque onset in the hybrids occurred 30-50% sooner than in the parental lines. Plaque numbers increased with age and plaques remained more numerous in the doubly transgenic animals at 9 and 12 months. Quantitative immunoassay via ELISA also showed an increase of total amyloid content in brain at 9-12 months. These histological and biochemical results support the conclusion that AChE may play a role in pathogenesis of Alzheimer's disease

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Rees T,Hammond PI,Soreq H,Younkin S,Brimijoin S

doi

10.1016/s0197-4580(02)00230-0

subject

Has Abstract

pub_date

2003-10-01 00:00:00

pages

777-87

issue

6

eissn

0197-4580

issn

1558-1497

pii

S0197458002002300

journal_volume

24

pub_type

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