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Basic Science and Pathogenesis
Sonal Kumar1,2, Annat Haber3, Catrina Spruce2
1Tufts University Graduate School of Biomedical Sciences, Boston, MA, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
Summary
Genetic factors, not just age, influence Alzheimer's disease (AD) biomarkers in marmosets. This study identifies potential genetic contributions to neurodegeneration, offering insights into human AD genetics.
Area of Science:
- Neuroscience
- Genetics
- Primate Models
Background:
- Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by genetic and environmental factors.
- Genome-wide studies have identified AD-associated variants, but the evolving polygenic risk over time remains unclear.
- Common marmosets offer a valuable nonhuman primate model for studying age-related neurodegeneration and AD pathology.
Purpose of the Study:
- To investigate genetic associations with plasma biomarkers related to Alzheimer's disease in a cohort of common marmosets.
- To explore the interplay between age, sex, and genetic factors in AD biomarker variation.
- To identify potential genetic loci contributing to neurodegeneration in a nonhuman primate model.
Main Methods:
- Whole genome sequencing of over 100 marmosets (wild-type and PSEN1 mutant carriers).
- Measurement of AD-associated plasma biomarkers (total tau, NfL, GFAP, beta-amyloid peptides).
- Linear mixed model analysis to assess genetic associations with individual and composite phenotypes, adjusting for kinship and sex.
Main Results:
- Females exhibited stronger correlations between neurodegeneration biomarkers (tTau, NfL, GFAP) and beta-amyloid peptides compared to males.
- A significant positive correlation between NfL and age was observed exclusively in male marmosets.
- Genome-wide scans identified numerous significant and suggestive single nucleotide polymorphisms (SNPs) associated with AD biomarkers.
Conclusions:
- Age alone does not fully explain variations in AD-relevant biomarkers in marmosets, indicating a substantial genetic influence.
- Heritable associations discovered in marmosets can provide valuable genetic insights into human AD progression and biology.
- Further investigation into the functional impacts of identified genetic loci is warranted.
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