Cerebrospinal Fluid Proteomics Identifies Potential Biomarkers for Early-Onset Alzheimer's Disease.
J Alzheimers Dis
; 100(1): 261-277, 2024.
Article
en En
| MEDLINE
| ID: mdl-38848183
ABSTRACT
Background:
Early-onset Alzheimer's disease (EOAD) exhibits a notable degree of heterogeneity as compared to late-onset Alzheimer's disease (LOAD). The proteins and pathways contributing to the pathophysiology of EOAD still need to be completed and elucidated.Objective:
Using correlation network analysis and machine learning to analyze cerebrospinal fluid (CSF) proteomics data to identify potential biomarkers and pathways associated with EOAD.Methods:
We employed mass spectrometry to conduct CSF proteomic analysis using the data-independent acquisition method in a Chinese cohort of 139 CSF samples, including 40 individuals with normal cognition (CN), 61 patients with EOAD, and 38 patients with LOAD. Correlation network analysis of differentially expressed proteins was performed to identify EOAD-associated pathways. Machine learning assisted in identifying crucial proteins differentiating EOAD. We validated the results in an Western cohort and examined the proteins expression by enzyme-linked immunosorbent assay (ELISA) in additional 9 EOAD, 9 LOAD, and 9 CN samples from our cohort.Results:
We quantified 2,168 CSF proteins. Following adjustment for age and sex, EOAD exhibited a significantly greater number of differentially expressed proteins than LOAD compared to CN. Additionally, our data indicates that EOAD may exhibit more pronounced synaptic dysfunction than LOAD. Three potential biomarkers for EOAD were identified SH3BGRL3, LRP8, and LY6âH, of which SH3BGRL3 also accurately classified EOAD in the Western cohort. LY6âH reduction was confirmed via ELISA, which was consistent with our proteomic results.Conclusions:
This study provides a comprehensive profile of the CSF proteome in EOAD and identifies three potential EOAD biomarker proteins.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores
/
Proteómica
/
Enfermedad de Alzheimer
Límite:
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos