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.
authors.affiliation: Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, Kansas City, MO, 64108, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Kaja
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sumien
authors.forename: Vidhi V
authors.initials: VV
authors.lastname: Shah
authors.forename: Imran
authors.initials: I
authors.lastname: Puthawala
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Maynard
authors.forename: Nitasha
authors.initials: N
authors.lastname: Khullar
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Payne
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forster
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
mesh_terms: D000375:Aging / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D053764:Presenilin-1 / Q000378:metabolism*; D053766:Presenilin-2 / Q000378:metabolism*; D065852:Spatial Memory
chemical_list: D008562:Membrane Glycoproteins; D053764:Presenilin-1; D053766:Presenilin-2; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases