Quantitative histological analysis of amyloid deposition in Alzheimer's double transgenic mouse brain

T. M. Wengenack, S. Whelan, G. L. Curran, K. E. Duff, J. F. Poduslo

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

The development of transgenic mice has created new opportunities for the generation of animal models of human neurodegenerative diseases where previously there was no animal counterpart. The first successful transgenic mouse model of Alzheimer's disease expressed increased levels of mutant human amyloid precursor protein, exhibiting neuritic-type amyloid deposits and behavioral deficits at six to nine months of age. More recently, it was shown that transgenic mice expressing both mutant human amyloid precursor protein and presenilin 1 exhibit neuritic-type amyloid deposits and behavioral deficits in as little as 12weeks. This accelerated Alzheimer phenotype greatly reduces the time necessary to conduct preclinical drug trials, as well as animal housing costs. The purpose of this study was to quantify the deposition of amyloid in five regions of the cortex and two regions of the hippocampus of transgenic mice expressing amyloid precursor protein (K670N, M671L) and presenilin 1 (M146L) mutations at various ages, using quantitative methods of confocal laser scanning microscopy and image analysis. Amyloid burden, expressed as the percentage area occupied by thioflavin S-positive amyloid deposits, increased an average of 179-fold from 12 to 54weeks of age (0.02±0.01% to 3.57±0.29%, mean±S.E.M., respectively) in five regions of the cortex and two of the hippocampus. This was a function of increases in both deposit number and size.This transgenic mouse provides an ideal animal model for evaluating the efficacy of potential therapeutic agents aimed at reducing amyloid deposition, such as inhibitors of amyloid fibril formation or secretase inhibitors. Copyright (C) 2000 IBRO.

Original languageEnglish (US)
Pages (from-to)939-944
Number of pages6
JournalNeuroscience
Volume101
Issue number4
DOIs
StatePublished - Nov 30 2000

Keywords

  • Animal model
  • Confocal laser microscopy
  • Hippocampus
  • Image analysis
  • Neuritic plaque
  • Thioflavin S

ASJC Scopus subject areas

  • Neuroscience(all)

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