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

被引：2
作者：
Abiose, Olamide [1 ,2 ,9 ]
Rutledge, Jarod [3 ,4 ]
Moran-Losada, Patricia [1 ,2 ,3 ]
Belloy, Michael E. [1 ]
Wilson, Edward N. [1 ,2 ]
He, Zihuai [1 ,5 ]
Trelle, Alexandra N. [1 ]
Channappa, Divya [1 ]
Romero, America [1 ]
Park, Jennifer [1 ]
Yutsis, Maya V. [1 ]
Sha, Sharon J. [1 ]
Andreasson, Katrin I. [1 ,2 ,6 ]
Poston, Kathleen L. [1 ,2 ,3 ]
Henderson, Victor W. [1 ,7 ]
Wagner, Anthony D. [2 ,8 ]
Wyss-Coray, Tony [1 ,2 ,3 ]
Mormino, Elizabeth C. [1 ,2 ,9 ]
机构：
[1] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Palo Alto, CA USA
[2] Stanford Univ, Sch Med, Wu Tsai Neurosci Inst, Stanford, CA USA
[3] Stanford Univ, Phil & Penny Knight Initiat Brain Resilience, Stanford, CA USA
[4] Stanford Univ, Dept Genet, Stanford, CA USA
[5] Stanford Univ, Sch Med, Ctr Biomed Informat Res, Stanford, CA USA
[6] Chan Zuckerberg Biohub, San Francisco, CA USA
[7] Stanford Univ, Sch Med, Dept Epidemiol & Populat Hlth, Stanford, CA USA
[8] Stanford Univ, Dept Psychol, Stanford, CA USA
[9] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, 453 Quarry Rd, Palo Alto, CA 94304 USA
来源：
ALZHEIMERS & DEMENTIA | 2024年 / 20卷 / 03期
关键词：
aging; Alzheimer's disease; autophagy; cerebral spinal fluid; clinically unimpaired; protein co-expression network; ubiquitination; AMYLOID-BETA; A-BETA; TAU; AUTOPHAGY; BRAIN; INDIVIDUALS; ASSOCIATION; BIOMARKERS; MECHANISM; PROTEINS;
D O I：
10.1002/alz.13576
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
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: beta = 2.44, p < 0.001, M7: beta = 2.57, p < 0.001) and executive function performance (M4: beta = -2.00, p = 0.005, M7: beta = -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.
引用
收藏
页码：1851 / 1867
页数：17
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