Age-related amyloid β deposition in transgenic mice overexpressing both alzheimer mutant presenilin 1 and amyloid β precursor protein swedish mutant is not associated with global neuronal loss

Ayano Takeuchi, Michael C. Irizarry, Karen Duff, Takaomi C. Saido, Karen Hsiao Ashe, Masato Hasegawa, David M.A. Mann, Bradley T. Hyman, Takeshi Iwatsubo

Research output: Contribution to journalArticle

199 Scopus citations

Abstract

To analyze the relationship between the deposition of amyloid β peptides (Aβ) and neuronal loss in transgenic models of Alzheimer's disease (AD), we examined the frontal neocortex (Fc) and CA1 portion of hippocampus (CA1) in PSAPP mice doubly expressing AD-associated mutant presenilin 1 (PS1) and Swedish-type mutant β amyloid precursor protein (APPsw) by morphometry of Aβ burden and neuronal counts. Deposition of Aβ was detected as early as 3 months of age in the Fc and CA1 of PSAPP mice and progressed to cover 28.3% of the superior frontal cortex and 18.4% of CA1 at 12 months: ˜20- (FC) and ˜40- (CA1) fold greater deposition than in APPsw mice. There was no significant difference in neuronal counts in either CA1 or the frontal cortex between nontransgenic (non-tg), PS1 transgenic, APPsw, and PSAPP mice at 3 to 12 months of age. In the PSAPP mice, there was disorganization of the neuronal architecture by compact amyloid plaques, and the average number of neurons was 8 to 10% fewer than the other groups (NS, P > 0.10) in CA1 and 2 to 20% fewer in frontal cortex (NS, P = 0.31). There was no loss of total synaptophysin immunoreactivity in the Fc or dentate gyrus molecular layer of the 12-month-old PSAPP mice. Thus, although co-expression of mutant PS1 with Swedish mutant βAPP leads to marked cortical and limbic Aβ deposition in an age-dependent manner, it does not result in the dramatic neuronal loss in hippocampus and association cortex characteristic of AD.

Original languageEnglish (US)
Pages (from-to)331-339
Number of pages9
JournalAmerican Journal of Pathology
Volume157
Issue number1
DOIs
StatePublished - Jan 1 2000

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