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Post-translational modifications linked to preclinical Alzheimer's disease-related pathological and cognitive changes.
Abiose, Olamide; Rutledge, Jarod; Moran-Losada, Patricia; Belloy, Michael E; Wilson, Edward N; He, Zihuai; Trelle, Alexandra N; Channappa, Divya; Romero, America; Park, Jennifer; Yutsis, Maya V; Sha, Sharon J; Andreasson, Katrin I; Poston, Kathleen L; Henderson, Victor W; Wagner, Anthony D; Wyss-Coray, Tony; Mormino, Elizabeth C.
Afiliação
  • Abiose O; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Rutledge J; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, California, USA.
  • Moran-Losada P; The Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
  • Belloy ME; Department of Genetics, Stanford University, Stanford, California, USA.
  • Wilson EN; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • He Z; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, California, USA.
  • Trelle AN; The Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, California, USA.
  • Channappa D; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Romero A; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Park J; Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, California, USA.
  • Yutsis MV; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Sha SJ; Center for Biomedical Informatics Research, Stanford University School of Medicine, Stanford, California, USA.
  • Andreasson KI; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Poston KL; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Henderson VW; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Wagner AD; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Wyss-Coray T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
  • Mormino EC; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Alzheimers Dement ; 20(3): 1851-1867, 2024 03.
Article em En | MEDLINE | ID: mdl-38146099
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 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).

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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Limite: Aged / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer / Disfunção Cognitiva Limite: Aged / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article