Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration.
Alzheimers Dement
; 2024 Aug 11.
Article
in 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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1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Alzheimers Dement
Year:
2024
Document type:
Article
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