Post‐translational modifications linked to preclinical Alzheimer's disease–related pathological and cognitive changes

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Abstract
INTRODUCTION: In this study, we leverage proteomic techniques to identify communities of proteins underlying Alzheimer's disease (AD) risk among clinically unimpaired (CU) older adults.METHODS: 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.RESULTS: We discovered modules enriched for phosphorylation and ubiquitination that were associated with abnormal amyloid status, as well as p‐tau181 (M4: β = 2.44, p < 0.001, M7: β = 2.57, p < 0.001) and executive function performance (M4: β = −2.00, p = 0.005, M7: β = −2.39, p < 0.001).DISCUSSION: 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.
Funding Information
  • National Institute on Aging (R01AG048076, R01AG74339, P50AG047366, P30AG066515, K99AG075238)

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