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Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes.

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Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes. Alzheimer's & dementia : the journal of the Alzheimer's Association Abiose, O., Rutledge, J., Moran-Losada, P., Belloy, M. E., Wilson, E. N., He, Z., Trelle, A. N., Channappa, D., Romero, A., Park, J., Yutsis, M. V., Sha, S. J., Andreasson, K. I., Poston, K. L., Henderson, V. W., Wagner, A. D., Wyss-Coray, T., Mormino, E. C. 2023

Abstract

In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults.We constructed a protein co-expression network using 3869 cerebrospinal fluid (CSF) proteins quantified by SomaLogic, Inc., in a cohort of participants along the AD clinical spectrum. We then replicated this network in an independent cohort of CU older adults and related these modules to clinically-relevant outcomes.We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p-tau181 (M4: ß = 2.44, p < 0.001, M7: ß = 2.57, p < 0.001) and executive function performance (M4: ß = -2.00, p = 0.005, M7: ß = -2.39, p < 0.001).In leveraging CSF proteomic data from individuals spanning the clinical spectrum of AD, we highlight the importance of post-translational modifications for early cognitive and pathological changes.

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