Alterations in β-amyloid production and deposition in brain regions of two transgenic models

Emily J H Lehman, Laura Shapiro Kulnane, Bruce Lamb

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Mutations in the amyloid precursor protein (APP) gene are associated with altered production and deposition of amyloid beta (Aβ) peptide in the Alzheimer's disease (AD) brain. The pathways that regulate APP processing, Aβ production and Aβ deposition in different tissues and brain regions remain unclear. To address this, we examined levels of various APP processing products as well as Aβ deposition in a genomic-based (R1.40) and a cDNA-based (Tg2576) transgenic mouse model of AD. In tissues, only brain generated detectable levels of the penultimate precursor to Aβ, APP C-terminal fragment-β. In brain regions, holoAPP levels remained constant, but ratios of APP C-terminal fragments and levels of Aβ differed significantly. Surprisingly, cortex had the lowest steady-state levels of Aβ compared to other brain regions. Comparison of Aβ deposition in Tg2576 and R1.40 animals revealed that R1.40 exhibited more abundant deposition in cortex while Tg2576 exhibited extensive deposition in the hippocampus. Our results suggest that AD transgenic models are not equal; their unique characteristics must be considered when studying AD pathogenesis and therapies.

Original languageEnglish (US)
Pages (from-to)645-653
Number of pages9
JournalNeurobiology of Aging
Volume24
Issue number5
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Amyloid
Amyloid beta-Protein Precursor
Alzheimer Disease
Brain
Protein C
Serum Amyloid A Protein
Amyloid beta-Peptides
Transgenic Mice
Hippocampus
Complementary DNA
Mutation
Genes
Therapeutics

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Amyloid-β
  • cDNA-based
  • Genomic-based
  • Transgenic mice

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Alterations in β-amyloid production and deposition in brain regions of two transgenic models. / Lehman, Emily J H; Kulnane, Laura Shapiro; Lamb, Bruce.

In: Neurobiology of Aging, Vol. 24, No. 5, 09.2003, p. 645-653.

Research output: Contribution to journalArticle

Lehman, Emily J H ; Kulnane, Laura Shapiro ; Lamb, Bruce. / Alterations in β-amyloid production and deposition in brain regions of two transgenic models. In: Neurobiology of Aging. 2003 ; Vol. 24, No. 5. pp. 645-653.
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