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Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration.
Duggan, Michael R; Yang, Zhijian; Cui, Yuhan; Dark, Heather E; Wen, Junhao; Erus, Guray; Hohman, Timothy J; Chen, Jingsha; Lewis, Alexandria; Moghekar, Abhay; Coresh, Josef; Resnick, Susan M; Davatzikos, Christos; Walker, Keenan A.
Afiliación
  • Duggan MR; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
  • Yang Z; Artificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Cui Y; Artificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Dark HE; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
  • Wen J; Laboratory of Artificial Intelligence and Biomedical Science, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
  • Erus G; Artificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Hohman TJ; Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Chen J; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
  • Lewis A; Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Moghekar A; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Coresh J; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Resnick SM; Departments of Population Health and Medicine, New York University Grossman School of Medicine, New York, New York, USA.
  • Davatzikos C; Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
  • Walker KA; Artificial Intelligence in Biomedical Imaging Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alzheimers Dement ; 20(9): 6486-6505, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39129354
ABSTRACT

INTRODUCTION:

Plasma proteomic analyses of unique brain atrophy patterns may illuminate peripheral drivers of neurodegeneration and identify novel biomarkers for predicting clinically relevant outcomes.

METHODS:

We identified proteomic signatures associated with machine learning-derived aging- and Alzheimer's disease (AD) -related brain atrophy patterns in the Baltimore Longitudinal Study of Aging (n = 815). Using data from five cohorts, we examined whether candidate proteins were associated with AD endophenotypes and long-term dementia risk.

RESULTS:

Plasma proteins associated with distinct patterns of age- and AD-related atrophy were also associated with plasma/cerebrospinal fluid (CSF) AD biomarkers, cognition, AD risk, as well as mid-life (20-year) and late-life (8-year) dementia risk. EFEMP1 and CXCL12 showed the most consistent associations across cohorts and were mechanistically implicated as determinants of brain structure using genetic methods, including Mendelian randomization.

DISCUSSION:

Our findings reveal plasma proteomic signatures of unique aging- and AD-related brain atrophy patterns and implicate EFEMP1 and CXCL12 as important molecular drivers of neurodegeneration. HIGHLIGHTS Plasma proteomic signatures are associated with unique patterns of brain atrophy. Brain atrophy-related proteins predict clinically relevant outcomes across cohorts. Genetic variation underlying plasma EFEMP1 and CXCL12 influences brain structure. EFEMP1 and CXCL12 may be important molecular drivers of neurodegeneration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Biomarcadores / Proteínas de la Matriz Extracelular / Proteómica / Quimiocina CXCL12 / Enfermedad de Alzheimer Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Biomarcadores / Proteínas de la Matriz Extracelular / Proteómica / Quimiocina CXCL12 / Enfermedad de Alzheimer Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Alzheimers Dement Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos