Memory deficits correlating with acetylcholinesterase splice shift and amyloid burden in doubly transgenic mice

Tina M. Rees, Amit Berson, Ella H. Sklan, Linda Younkin, Steven G Younkin, William Stephen Brimijoin, Hermona Soreq

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Current mouse models of Alzheimer's disease show brain pathology that correlates to a degree with memory impairment, but underlying molecular mechanisms remained unknown. Here we report studies with three lines of transgenic mice: animals that doubly express mutated human amyloid precursor protein (APPswe) and human acetylcholinesterase (hAChE); and animals transgenic for only the APPswe or the hAChE. Among these genotypes, variations were observed in expression of mRNA for presenilin-1, which was highest in singly transgenic hAChE mice, and the stress-inducible form of AChE, which was elevated when both transgenes were present. At the age of nine months, both double and single transgenic mice displayed working memory impairment in a radial arm water maze. However, as compared with mice expressing amyloid alone, the double transgenic animals exhibited more numerous plaques and greater amyloid burden in brain (both by histochemistry and by ELISA of amyloid protein). Moreover, the amyloid burden in double transgenics was tightly correlated with memory impairment as measured by total maze errors (r2 = 0.78, p = .002). This correlation was markedly stronger than observed in mice with amyloid alone. These new findings support the notion of cholinergic-amyloid interrelationships and highlight the double transgenic mice as a promising alternative for testing Alzheimer's therapies.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalCurrent Alzheimer Research
Volume2
Issue number3
DOIs
StatePublished - Jul 2005

Fingerprint

Memory Disorders
Acetylcholinesterase
Amyloid
Transgenic Mice
Genetically Modified Animals
Presenilin-1
Amyloidogenic Proteins
Amyloid beta-Protein Precursor
Amyloid Plaques
Brain
Transgenes
Short-Term Memory
Cholinergic Agents
Alzheimer Disease
Enzyme-Linked Immunosorbent Assay
Genotype
Pathology
Messenger RNA
Water
Therapeutics

Keywords

  • Acetylcholinesterase variants
  • Alzheimer's disease
  • Amyloid precursor protein
  • Cerebral cortex
  • Hippocampus
  • Presenilin1

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Memory deficits correlating with acetylcholinesterase splice shift and amyloid burden in doubly transgenic mice. / Rees, Tina M.; Berson, Amit; Sklan, Ella H.; Younkin, Linda; Younkin, Steven G; Brimijoin, William Stephen; Soreq, Hermona.

In: Current Alzheimer Research, Vol. 2, No. 3, 07.2005, p. 291-300.

Research output: Contribution to journalArticle

Rees, Tina M. ; Berson, Amit ; Sklan, Ella H. ; Younkin, Linda ; Younkin, Steven G ; Brimijoin, William Stephen ; Soreq, Hermona. / Memory deficits correlating with acetylcholinesterase splice shift and amyloid burden in doubly transgenic mice. In: Current Alzheimer Research. 2005 ; Vol. 2, No. 3. pp. 291-300.
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