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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

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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.

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Acknowledgments

Research reported in this publication was supported in part by grants AG022550, AG027956 (MJF, NS, and PK), and AG010485 from NIH/NIA and RR022570 and RR027093 from NIH/NCRR (PK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support by the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research, the Vision Research Foundation of Kansas City and a departmental challenge grant by Research to Prevent Blindness (PK) are gratefully acknowledged. The authors thank Margaret, Richard, and Sara Koulen for generous support and encouragement.

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Authors and Affiliations

  1. Vision Research Center, Department of Ophthalmology, University of Missouri - Kansas City, Kansas City, MO, 64108, USA

    Simon Kaja, Vidhi V. Shah, Imran Puthawala, Alexandra N. Maynard, Nitasha Khullar, Andrew J. Payne & Peter Koulen

  2. Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer’s Disease, Fort Worth, TX, 76107, USA

    Nathalie Sumien & Michael J. Forster

  3. Department of Basic Medical Science, School of Medicine, University of Missouri - Kansas City, Kansas City, MO, 64108, USA

    Peter Koulen

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  1. Simon Kaja
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Kaja, S., Sumien, N., Shah, V.V. et al. Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels. Mol Neurobiol 52, 545–554 (2015). https://doi.org/10.1007/s12035-014-8877-4

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