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Updated: Jan 7, 2026

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

Mina Idris1, Fedal Saini1, Phoebe Ivain1

  • 1King's College London, London, United Kingdom.

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

Individuals with Down syndrome (DS) show early Alzheimer's disease (AD) biomarker changes similar to other AD forms. An event-based model (EBM) helps sequence these changes, potentially enabling earlier diagnosis in DS.

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Area of Science:

  • Neurology
  • Biomarkers
  • Genetics

Background:

  • Individuals with Down syndrome (DS) have a significantly higher risk of developing Alzheimer's disease (AD), with pathology often emerging in their thirties.
  • The precise sequence of plasma biomarker, cognitive, and neuroimaging changes preceding clinical AD in DS is not well understood.
  • The event-based model (EBM) is a data-driven approach to estimate disease progression sequences from cross-sectional data, accounting for individual variability.

Purpose of the Study:

  • To apply the EBM to a cohort of adults with DS to determine the sequence of biomarker, cognitive, and neuroimaging changes before AD diagnosis.
  • To stage individuals with DS along this identified disease progression sequence.

Main Methods:

  • Utilized the event-based model (EBM) on data from 60 adults with Down syndrome (DS) and no current AD diagnosis.
  • Examined clinical assessments, plasma biomarkers (e.g., amyloid-beta 42/40 ratio, p-tau, NfL, GFAP), and will incorporate structural MRI data.
  • Aims to establish a multi-modal sequence of preclinical AD changes.

Main Results:

  • Preliminary findings indicate that early AD changes in DS mirror those in sporadic and familial AD.
  • Observed sequence: altered plasma amyloid-beta 42/40 ratio, followed by memory decline, neurodegeneration markers (p-tau, NfL), executive dysfunction, visuomotor deficits, and later neuroinflammation (GFAP).
  • Structural MRI data will be integrated to refine the multi-modal progression sequence.

Conclusions:

  • This research refines the understanding of AD progression timing in DS, aiding in optimizing cognitive testing, neuroimaging, and blood sampling strategies.
  • The EBM provides individual-level staging, which could facilitate earlier diagnosis and improve clinical trial design for AD in the DS population.
  • Integrating multiple data modalities (plasma biomarkers, cognitive, neuroimaging) offers deeper insights into preclinical AD stages in individuals with DS.