Artifactual strain-specific signs of incipient brain amyloidosis in APP transgenic mice

S. M. Ali, S. L. Siedlak, P. A. Gonzalez-DeWhitt, R. A. Altman, J. M. Glendening, D. E. Lowery, M. J. Savage, H. G. Polites, G. Perry, B. D. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

In an attempt to generate trans,oenic mice modeling Alzheimer-type amyloidogenesis, the COOH-terminal 103 residue human APP segment was expressed in brain regions known to be vulnerable in AD. Transfected cells overexpressing this transgene were previously shown to develop intracytoplasmic inclusions that were immunoreactive with antibodies to the APP COOH-terminus. Transgenic C57BG/SJL mice produced transgene-coded mRNA in their brains at levels up to sixfold above endogenous APP, most abundantly within cortical and hippocampal pyramidal neurons. Immunocytochemistry with anti-Aβ antibodies revealed occasional structures that resembled diffuse amyloid, but which could not be detected on serial sections. Immunolabeling with antibodies to APP regions NH2-terminal to the transgene-coded domain revealed elevated immunoreactivity within perikarya and neurites in regions expressing the highest transgene and endogenous APP mRNA levels, similar to observations previously reported within vulnerable neurons in AD brain. However, subsequent breeding revealed that this phenotype segregated with the B6/SJL background rather than the transgene, thus emphasizing the importance of genetic background to observations of putative AD-type pathology in transgenic animals.

Original languageEnglish (US)
Pages (from-to)223-234
Number of pages12
JournalNeurobiology of aging
Volume17
Issue number2
DOIs
StatePublished - 1996
Externally publishedYes

Keywords

  • Alzheimer's Discase
  • Amyloid precursor protein
  • Immunocytochemistry
  • In situ hybridization
  • Pathology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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