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

Afonso C Silva1, Jung Eun Park1, Gregg E Homanics1

  • 1University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed gene-edited marmoset models for Alzheimer's disease (AD) research. These models show early signs of AD pathology, aiding the study of primate-specific disease mechanisms.

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Area of Science:

  • Neuroscience
  • Genetics
  • Primate Models

Background:

  • Established the MARMO-AD consortium to create and validate marmosets as Alzheimer's disease (AD) models.
  • Focuses on gene-edited marmosets carrying AD-causative mutations, compared to wild-type aging marmosets.
  • Addresses limitations of existing models for studying primate-specific AD pathogenesis.

Purpose of the Study:

  • To develop and characterize gene-edited marmoset models for Alzheimer's disease research.
  • To investigate primate-specific mechanisms in AD onset and progression.
  • To facilitate translational studies for accelerated therapeutic development.

Main Methods:

  • Utilized CRISPR/Cas9 to introduce PSEN1 mutations (C410Y, A426P) in marmosets.
  • Conducted lifespan studies with non-invasive longitudinal assessments (behavioral, biomarker, neuroimaging, multiomics).
  • Characterized genetic, molecular, functional, behavioral, cognitive, and pathological features.

Main Results:

  • Successfully generated viable marmosets with C410Y- and A426P-PSEN1 mutations, with germline transmission confirmed for C410Y.
  • PSEN1 mutation carriers exhibited elevated plasma amyloid beta before adulthood.
  • Observed alterations in gamma-secretase complex enzyme-substrate interactions in the brain.

Conclusions:

  • Marmoset models offer a unique platform to study primate-specific cellular and molecular factors in AD.
  • This approach overcomes limitations of other model organisms.
  • Facilitates translational research for developing novel Alzheimer's therapies.