Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex

T. Rees, P. I. Hammond, H. Soreq, Steven G Younkin, William Stephen Brimijoin

Research output: Contribution to journalArticle

155 Citations (Scopus)

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/Nx[C57B6xSJL/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

Original languageEnglish (US)
Pages (from-to)777-787
Number of pages11
JournalNeurobiology of Aging
Volume24
Issue number6
DOIs
StatePublished - Oct 2003

Fingerprint

Amyloid Plaques
Acetylcholinesterase
Cerebral Cortex
Amyloid
Alzheimer Disease
Brain
Genetically Modified Animals
Amyloid beta-Protein Precursor
Transgenes
Immunoassay
Transgenic Mice
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

Keywords

  • Alzheimer's disease
  • Amyloid beta 1-42
  • Amyloid precursor protein
  • Doubly transgenic mice
  • Microglial activation
  • Tg2576

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. / Rees, T.; Hammond, P. I.; Soreq, H.; Younkin, Steven G; Brimijoin, William Stephen.

In: Neurobiology of Aging, Vol. 24, No. 6, 10.2003, p. 777-787.

Research output: Contribution to journalArticle

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