Abstract
INTRODUCTION
Alzheimer’s disease (AD) is the leading cause of dementia, affecting around 50 million individuals worldwide. Brain-derived extracellular vesicles (EVs) can cross the blood–brain barrier carrying neuron-specific molecules, such as microRNAs (miRNAs), which have potential as biomarkers of neurodegeneration.
METHODS
We explored the association between neuronal-derived EV miRNAs from serum and AD clinical status by performing a transcriptome-wide association study involving 46 participants with clinical AD, 14 participants with preclinical AD, and 60 neurologically healthy controls.
RESULTS
We identified 14 miRNAs associated with AD risk, with more pronounced transcriptional alterations in preclinical individuals compared to clinical AD individuals. Functional analysis revealed enrichment of miRNA-target genes in neurodegenerative pathways, highlighting synuclein alpha (SNCA), cytochrome c, somatic (CYCS), and microtubule associated protein tau (MAPT) as key targets.
DISCUSSION
Our results highlight the potential role of neuronal-derived EVs in neurodegeneration and suggest avenues for further research into brain-derived biomarkers.
Highlights
Neuronal-derived extracellular vesicles (NDEVs) carry potential brain biomarkers.
We tested the association between NDEV microRNAs (miRNAs) and Alzheimer’s disease (AD).
Fourteen NDEV miRNAs were associated with AD.
Preclinical AD displayed more pronounced transcriptional changes than clinical AD.
miRNA-target genes were enriched in pathways associated with neurodegeneration.
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This post is Copyright: Paolo Reho,
Vrinda Kalia,
Gabriela L. Jackson,
Fang Wang,
Erez Eiten,
Kasey Brennan,
Adam M. Brickman,
Richard Mayeux,
Gary W. Miller,
Badri N. Vardarajan,
Andrea Baccarelli,
Haotian Wu | March 5, 2025