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

页码：1851 / 1867

页数：17

共 50 条

[1] Tau Post-Translational Modifications: Potentiators of Selective Vulnerability in Sporadic Alzheimer's Disease
Carroll, Trae
Guha, Sanjib
Nehrke, Keith
Johnson, Gail V. W.
BIOLOGY-BASEL, 2021, 10 (10):
[2] Post-translational modifications of tau protein in Alzheimer's disease
Gong, CX
Liu, F
Grundke-Iqbal, I
Iqbal, K
JOURNAL OF NEURAL TRANSMISSION, 2005, 112 (06) : 813 - 838
[3] Role of Post-translational Modifications in Alzheimer's Disease
Ramesh, Madhu
Gopinath, Pushparathinam
Govindaraju, Thimmaiah
CHEMBIOCHEM, 2020, 21 (08) : 1052 - 1079
[4] Post-Translational Modifications in Alzheimer's Disease and the Potential for New Biomarkers
Russell, Claire L.
Koncarevic, Sasa
Ward, Malcolm A.
JOURNAL OF ALZHEIMERS DISEASE, 2014, 41 (02) : 345 - 364
[5] Post-Translational Modifications of BACE1 in Alzheimer's Disease
Wen, Wen
Li, Ping
Liu, Panwang
Xu, Shijun
Wang, Fushun
Huang, Jason H.
CURRENT NEUROPHARMACOLOGY, 2022, 20 (01) : 211 - 222
[6] Post-translational modifications of Parkinson's disease-related proteins: Phosphorylation, SUMOylation and Ubiquitination
Junqueira, Stella C.
Centeno, Eduarda G. Z.
Wilkinson, Kevin A.
Cimarosti, Helena
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2019, 1865 (08): : 2001 - 2007
[7] Post-translational modifications of tau protein: Implications for Alzheimer's disease
Martin, Ludovic
Latypova, Xenia
Terro, Faraj
NEUROCHEMISTRY INTERNATIONAL, 2011, 58 (04) : 458 - 471
[8] Dissecting Alzheimer's Disease Molecular Substrates by Proteomics and Discovery of Novel Post-translational Modifications
Deolankar, Sayali Chandrashekhar
Patil, Arun H.
Koyangana, Shashanka G.
Subbannayya, Yashwanth
Prasad, Thottethodi Subrahmanya Keshava
Modi, Prashant Kumar
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY, 2019, 23 (07) : 350 - 361
[9] JUMPptm: Integrated software for sensitive identification of post-translational modifications and its application in Alzheimer's disease study
Poudel, Suresh
Vanderwall, David
Yuan, Zuo-Fei
Wu, Zhiping
Peng, Junmin
Li, Yuxin
PROTEOMICS, 2023, 23 (3-4)
[10] Histone post-translational modifications in frontal cortex from human donors with Alzheimer's disease
Anderson, Kyle W.
Turko, Illarion V.
CLINICAL PROTEOMICS, 2015, 12

← 1 2 3 4 5 →