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

Sophie E Mastenbroek1,2,3, Lyduine E Collij1,2,3, Jacob W Vogel4

  • 1Amsterdam Neuroscience, Brain Imaging, Amsterdam, Netherlands.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
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Summary
This summary is machine-generated.

A new two-step workflow using smell tests and CSF α-synuclein seed amplification assays accurately identifies Lewy body pathology, reducing invasive testing needs.

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Area of Science:

  • Neuroscience
  • Biomarker Discovery
  • Neuropathology

Background:

  • Cerebrospinal fluid (CSF) seed amplification assays (SAAs) are effective in detecting α-synuclein (αsyn) seeds for Lewy body pathology (LBP).
  • CSF sampling is invasive, costly, and time-consuming, hindering widespread clinical application.
  • A neuropathologically-validated two-step workflow combining smell function and CSF αsyn SAA was developed to improve LBP diagnosis.

Purpose of the Study:

  • To develop and evaluate a two-step workflow for accurate postmortem determination of Lewy body pathology (LBP) status.
  • To assess the workflow's performance across diverse clinical groups, including those with parkinsonism, Alzheimer's disease (AD) syndromes, and clinically unimpaired individuals.
  • To determine the potential reduction in the need for confirmatory CSF testing.

Main Methods:

  • A cohort of 358 individuals underwent antemortem smell testing (UPSIT), CSF αsyn SAA, and postmortem neuropathological assessment.
  • Step 1 involved a risk-stratification model using UPSIT scores, age, and sex to predict cortical LBP.
  • Step 2 applied confirmatory CSF αsyn SAA only to high-risk individuals, with performance evaluated across the entire cohort and specific subgroups.

Main Results:

  • The two-step workflow demonstrated high accuracy (93-95%) in identifying cortical LBP across all evaluated groups.
  • It significantly reduced CSF testing requirements, ranging from -23% to -80% depending on the clinical subgroup.
  • Positive predictive values ranged from 75-96%, and negative predictive values ranged from 95-98%, with high performance in specific subgroups like clinical parkinsonism and clinical AD.

Conclusions:

  • A two-step workflow integrating smell function and CSF αsyn SAA offers a less invasive and potentially more cost-effective method for diagnosing LBP.
  • This approach can reduce the burden of invasive procedures like lumbar punctures for patients and healthcare systems.
  • The workflow's high accuracy and efficiency support its implementation in various clinical settings for improved LBP assessment.