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

Neuroscience. 2000;101(4):939-44. doi: 10.1016/s0306-4522(00)00388-2.


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 12 weeks. 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 54 weeks 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / metabolism*
  • Brain / pathology*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Image Processing, Computer-Assisted
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics
  • Microscopy, Confocal
  • Presenilin-1


  • Amyloid
  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • PSEN1 protein, human
  • Presenilin-1