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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Vijaya L Reddy1, Jesse M Cedarbaum1, John Seibyl1

  • 1Yale University School of Medicine, New Haven, CT, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

In REM sleep behavior disorder (RBD), dopamine transporter (DaT) positivity links to cognitive decline, while alpha-synuclein (αSyn) positivity surprisingly correlates with better cognitive function in this preclinical synucleinopathy stage.

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Area of Science:

  • Neuroscience
  • Neurology
  • Biomarker Research

Background:

  • Alpha-synuclein (αSyn) protein is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's.
  • Elevated cerebrospinal fluid (CSF) αSyn seeding activity and reduced striatal dopaminergic activity are linked to cognitive decline in synucleinopathies.
  • REM sleep behavior disorder (RBD) is a preclinical stage of synucleinopathy, making it a key focus for early detection.

Purpose of the Study:

  • To investigate the relationship between CSF αSyn aggregation and striatal dopaminergic deficits in RBD patients.
  • To assess the impact of these factors on cognitive performance in individuals with RBD.
  • To explore potential biomarkers for predicting phenoconversion to clinical synucleinopathy.

Main Methods:

  • Thirty-five RBD participants (aged 51-80, MoCA >23) underwent 123-I ioflupane SPECT dopamine transporter (DaT) scans and lumbar punctures.
  • CSF αSyn levels were analyzed, and participants were categorized based on DaT scan results (DaT-positive, intermediate, negative).
  • Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and additional tests in a subset of participants.

Main Results:

  • CSF αSyn positivity was observed in 71% of participants (25/35).
  • DaT positivity was associated with lower cognitive scores, though not statistically significant.
  • αSyn-positive participants showed significantly higher working memory index and MoCA scores compared to αSyn-negative participants (p=0.05).

Conclusions:

  • DaT positivity in RBD may indicate cognitive impairment, aligning with synucleinopathy progression.
  • Unexpectedly, αSyn positivity in this cohort correlated with better cognitive performance.
  • Further research is needed to validate these biomarkers for predicting phenoconversion to clinical synucleinopathy.