Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels

Simon Kaja, Nathalie Sumien, Vidhi V. Shah, Imran Puthawala, Alexandra N. Maynard, Nitasha Khullar, Andrew J. Payne, Michael J. Forster, Peter Koulen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mutations in presenilin (PS) proteins cause familial Alzheimer’s disease. We herein tested the hypothesis that the expression levels of PS proteins are differentially affected during healthy aging, in the absence of pathological mutations. We used a preclinical model for aging to identify associations between PS expression and quantitative behavioral parameters for spatial memory and learning and motor function. We identified significant changes of PS protein expression in both cerebellum and forebrain that correlated with the performance in behavioral paradigms for motor function and memory and learning. Overall, PS1 levels were decreased, while PS2 levels were increased in aged mice compared with young controls. Our study presents novel evidence for the differential expression of PS proteins in a nongenetic model for aging, resulting in an overall increase of the PS2 to PS1 ratio. Our findings provide a novel mechanistic basis for molecular and functional changes during normal aging.

Original languageEnglish
Pages (from-to)545-554
Number of pages10
JournalMolecular Neurobiology
Volume52
Issue number1
DOIs
StatePublished - 25 Aug 2015

Fingerprint

Presenilin-2
Presenilins
Presenilin-1
Brain
Proteins
Mutation
Prosencephalon
Cerebellum
Alzheimer Disease
Spatial Memory
Spatial Learning
Learning

Keywords

  • Aging
  • Alzheimer’s disease
  • Behavior
  • Behavior
  • Calcium
  • Cerebellum
  • Cognition
  • Cognitive performance
  • Motor learning
  • Neurodegeneration
  • Neuron

Cite this

Kaja, Simon ; Sumien, Nathalie ; Shah, Vidhi V. ; Puthawala, Imran ; Maynard, Alexandra N. ; Khullar, Nitasha ; Payne, Andrew J. ; Forster, Michael J. ; Koulen, Peter. / Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels. In: Molecular Neurobiology. 2015 ; Vol. 52, No. 1. pp. 545-554.
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Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels. / Kaja, Simon; Sumien, Nathalie; Shah, Vidhi V.; Puthawala, Imran; Maynard, Alexandra N.; Khullar, Nitasha; Payne, Andrew J.; Forster, Michael J.; Koulen, Peter.

In: Molecular Neurobiology, Vol. 52, No. 1, 25.08.2015, p. 545-554.

Research output: Contribution to journalArticle

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