Cortical proteins may provide motor resilience in older adults

Buchman, Aron S.; Yu, Lei; Oveisgharan, Shahram; Petyuk, Vladislav A.; Tasaki, Shinya; Gaiteri, Chris; Wilson, Robert S.; Grodstein, Francine; Schneider, Julie A.; Klein, Hans-Ulrich; De Jager, Philip L.; Bennett, David A.

doi:10.1038/s41598-021-90859-3

Cortical proteins may provide motor resilience in older adults

Journal Article · Fri May 28 00:00:00 EDT 2021 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-021-90859-3· OSTI ID:1815689

Buchman, Aron S. ^[1]; Yu, Lei ^[2]; Oveisgharan, Shahram ^[2]; Petyuk, Vladislav A. ^[3]; Tasaki, Shinya ^[2]; Gaiteri, Chris ^[2]; Wilson, Robert S. ^[4]; Grodstein, Francine ^[5]; Schneider, Julie A. ^[6]; Klein, Hans-Ulrich ^[7]; De Jager, Philip L. ^[7]; Bennett, David A. ^[2]

Rush Univ. Medical Center, Chicago, IL (United States). Rush Alzheimer's Disease Center; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Neurological Sciences; OSTI
Rush Univ. Medical Center, Chicago, IL (United States). Rush Alzheimer's Disease Center; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Neurological Sciences
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Division
Rush Univ. Medical Center, Chicago, IL (United States). Rush Alzheimer's Disease Center; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Neurological Sciences; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Psychiatry and Behavioral Sciences
Rush Univ. Medical Center, Chicago, IL (United States). Rush Alzheimer's Disease Center; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Internal Medicine
Rush Univ. Medical Center, Chicago, IL (United States). Rush Alzheimer's Disease Center; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Neurological Sciences; Rush Univ. Medical Center, Chicago, IL (United States). Dept. of Pathology
Columbia Univ., New York, NY (United States). Medical Center, Center for Translational & Computational Neuroimmunology, Dept. of Neurology

Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Institute on Aging (NIA); USDOE Office of Science (SC)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1815689

Alternate ID(s):: OSTI ID: 2998801

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 11; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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