Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits

Acta Neuropathol Commun. 2015 Nov 14;3:72. doi: 10.1186/s40478-015-0252-9.

Abstract

Introduction: Transgenic overexpression of amyloid precursor protein (APP) genes that are either entirely human in sequence or have humanized Aβ sequences can produce Alzheimer-type amyloidosis in mice, provided the transgenes also encode mutations linked to familial Alzheimer's Disease (FAD). Although transgenic mice have been produced that overexpress wild-type mouse APP, no mice have been generated that express mouse APP with FAD mutations. Here we describe two different versions of such mice that produce amyloid deposits consisting of entirely of mouse Aβ peptides. One line of mice co-expresses mouse APP-Swedish (moAPPswe) with a human presenilin exon-9 deleted variant (PS1dE9) and another line expresses mouse APP-Swedish/Indiana (APPsi) using tetracycline-regulated vectors (tet.moAPPsi).

Results: Both lines of mice that produce mouse Aβ develop amyloid deposits, with the moAPPswe/PS1dE9 mice developing extracellular compact, cored, neuritic deposits that primarily localize to white matter tracts and meningial layers, whereas the tet.moAPPsi mice developed extracellular diffuse cortical/hippocampal deposits distributed throughout the parenchyma.

Conclusions: These findings demonstrate that murine Aβ peptides have the capacity to produce amyloid deposits that are morphologically similar to deposits found in human AD provided the murine APP gene harbors mutations linked to human FAD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression Regulation / genetics*
  • Glial Fibrillary Acidic Protein
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Neuroblastoma / pathology
  • Plaque, Amyloid / metabolism*
  • Presenilin-1 / genetics*
  • Presenilin-1 / metabolism

Substances

  • Amyloid beta-Peptides
  • Glial Fibrillary Acidic Protein
  • Presenilin-1
  • Green Fluorescent Proteins