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

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Authors: Kaja, S.; Sumien, N.; Shah, V. V.; Puthawala, I.; Maynard, A. N.; Khullar, N.; Payne, A. J.; Forster, M. J.; Koulen, P.
Article Title: Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels
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.
Journal Title: Molecular neurobiology
Volume: 52
Issue: 1
ISSN: 1559-1182; 0893-7648
Publisher: Unknown  
Journal Place: United States
Date Published: 2015
Start Page: 545
End Page: 554
Language: ENG
DOI/URL:

10.1007/s12035-014-8877-4
Notes: LR: 20161019; GR: P01 AG022550/AG/NIA NIH HHS/United States; GR: P01 AG027956/AG/NIA NIH HHS/United States; GR: AG010485/AG/NIA NIH HHS/United States; GR: AG022550/AG/NIA NIH HHS/United States; GR: P01 AG010485/AG/NIA NIH HHS/United States; GR: RR022570/RR/NCRR NIH HHS/United States; GR: AG027956/AG/NIA NIH HHS/United States; GR: S10 RR027093/RR/NCRR NIH HHS/United States; GR: S10 RR022570/RR/NCRR NIH HHS/United States; GR: RR027093/RR/NCRR NIH HHS/United States; JID: 8900963; 0 (Membrane Glycoproteins); 0 (Presenilin-1); 0 (Presenilin-2); 0 (nicastrin protein); EC 3.4.- (Amyloid Precursor Protein Secretases); NIHMS627274; OID: NLM: NIHMS627274; OID: NLM: PMC4362879; 2014/06/20 [received]; 2014/08/25 [accepted]; ppublish