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Exploring cerebrospinal fluid metabolites, cognitive function, and brain atrophy: Insights from Mendelian
Qian Liu1, Ling-Bing Meng2, Tian-Qi Qi1
1Department of Clinical Laboratory, Aerospace Center Hospital, Beijing, 100049, China.
Open Medicine (Warsaw, Poland)
|August 7, 2025
Summary
Cerebrospinal fluid (CSF) metabolites causally influence brain structure and cognitive function. This study identifies specific metabolites linked to brain atrophy and cognitive performance, offering potential therapeutic targets for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Metabolomics
- Genetics
Background:
- Cerebrospinal fluid (CSF) metabolite disruptions are linked to altered brain function, cognition, and structure.
- Understanding the causal links between CSF metabolites and neurological outcomes is crucial for developing effective interventions.
Purpose of the Study:
- To investigate the causal relationships between cerebrospinal fluid (CSF) metabolites and neurological outcomes, including cognitive performance and brain structure.
- To identify specific CSF metabolites that may serve as therapeutic targets for neurodegenerative diseases.
Main Methods:
- A two-sample Mendelian randomization analysis was performed.
- Genome-wide association data for metabolites (N=689) were analyzed with data for cognitive performance (N=257,841), brain atrophy (N=51,665), and hippocampal volume (N=33,536).
Main Results:
- Thirty metabolites showed causal associations with brain atrophy and/or cognitive function.
- Specific metabolites were linked to cortical surface area (butyrate), cortical thickness (bilirubin), hippocampal volume (methionine sulfoxide), and cognitive measures (threonate, oxidized Cys-gly, N6-succinyladenosine, N-acetylglucosamine).
- Butanoate and niacinamide/niacin ester metabolism pathways were significantly associated with brain atrophy and cognitive performance.
Conclusions:
- CSF metabolites have a causal impact on brain structure and cognitive function.
- Specific metabolites and metabolic pathways represent promising targets for therapeutic interventions in neurodegenerative diseases.
- Genetic evidence supports further experimental investigation into these metabolic pathways for neurodegeneration treatment.
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