ArticleAlzheimer's & dementia (New York, N. Y.)
Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease.
Article in Alzheimer's & dementia (New York, N. Y.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Functionally informed annotation influences pathway-specific polygenic risk and disease inference in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Transcriptome profiling of cerebrospinal fluid in Alzheimer's disease reveals molecular dysregulations associated with disease.Alzheimer's & dementia (New York, N. Y.)Article
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Abstract
backgroundDespite the increasing prevalence of neurodegenerative diseases, the molecular characterization of brain pathologies remains challenging due to limited tissue access. Cerebrospinal fluid (CSF) contains a significant proportion of brain-derived molecular contents, and characterizing these molecules has served as a proxy for evaluating molecular dysregulation in the brain. Here we have characterized the CSF cell-free messenger RNA (cf-mRNA) transcriptome and identified genes and pathways altered in Alzheimer's disease (AD).
methodsWe performed cf-mRNA sequencing on 52 human CSF samples and further compared their transcriptomic profiles to matched plasma samples. In addition, we also investigated the cf-mRNA profiles of CSF in individuals with AD as well as non-cognitively impaired (NCI) controls.
resultsThe molecular content of CSF cf-mRNA was distinct from that of plasma cf-mRNA, with a substantially higher number of brain-associated genes identified in CSF. A large set of dysregulated gene transcripts from CSF was detected in the AD subjects, and these gene transcripts were able to discriminate AD from NCI subjects. Notably, the gene transcripts were enriched in biological processes closely associated with AD, such as brain development and synaptic signaling. In addition, we discovered a subset of gene transcripts that exhibited a high correlation in matched CSF and plasma samples from AD subjects.
conclusionsThis study not only reveals the novel cf-mRNA content of CSF but also highlights the potential of CSF cf-mRNA profiling as a tool to garner pathophysiological insights into AD. Highlights: Cell-free messenger RNA (cf-mRNA) sequencing was performed on 52 human cerebrospinal fluid (CSF) samples.CSF exhibited a distinct transcriptional profile with a higher prevalence of brain-associated genes compared to plasma.Dysregulated genes in Alzheimer's disease (AD) CSF effectively distinguished AD from non-cognitively impaired controls.CSF cf-mRNA profiling holds potential as a tool for gaining pathophysiological insights into AD.
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