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Cerebrospinal fluid proteins in relation to longitudinal cognitive trajectories
Bo-Hyun Kim1, Sang Won Seo1,2,3,4,5, JunPyo Kim1,2,3
1Alzheimer's Disease Convergence Research Center, Samsung Medical Center, Seoul, Republic of Korea.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|November 11, 2025
Summary
Cerebrospinal fluid (CSF) protein levels in Alzheimer's disease (AD) correlate with cognitive function and its decline over time. These protein signatures offer molecular insights into cognitive trajectories.
Area of Science:
- Neuroscience
- Proteomics
- Biochemistry
Background:
- Alzheimer's disease (AD) is characterized by progressive cognitive decline.
- Understanding the molecular underpinnings of cognitive trajectories in AD is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the relationship between cerebrospinal fluid (CSF) proteomics and longitudinal cognitive trajectories in Alzheimer's disease (AD).
- To identify specific protein signatures and pathways associated with cognitive decline and its changes over time.
Main Methods:
- Differential protein abundance analysis of CSF proteomics data (SomaScan 7K) was performed.
- Analysis correlated protein levels with composite scores for memory (MEM), executive function (EF), and language (LAN), and their longitudinal changes.
- Co-abundance network analysis, functional enrichment, and machine learning were employed to identify protein modules, pathways, and predictive models.
Main Results:
- Proteins associated with memory and executive function were enriched in microglia and oligodendrocytes, respectively.
- Identified protein signatures and pathways linked to longitudinal cognitive decline.
- A predictive model for cognitive decline trajectories achieved an area under the curve of up to 0.79, with a 30.9% improvement in prediction performance.
Conclusions:
- CSF protein alterations are associated with baseline cognitive function and longitudinal changes in cognitive decline in AD.
- Specific protein signatures and their associated biological pathways provide molecular insights into cognitive trajectories in AD.
- These findings highlight the potential of CSF proteomics for understanding and predicting cognitive changes in Alzheimer's disease.
Keywords:
Alzheimer's diseasecerebrospinal fluidcognitive trajectorydifferential protein abundancemachine learningproteomicsMore Related Videos
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