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

Kaitlin B Casaletto1, Rowan Saloner2

  • 1Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.

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

Menopause timing influences Alzheimer's disease (AD) risk, particularly tau pathology. Plasma proteomics revealed that age at menopause is linked to immune, synaptic, and tau biomarkers, with AGRN potentially explaining female vulnerability to tau.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Genomics

Background:

  • Females have a two-fold higher risk of Alzheimer's disease (AD).
  • Early menopause is linked to increased AD risk and tau pathology.
  • Investigating female biology may reveal AD insights and address knowledge gaps.

Purpose of the Study:

  • To identify plasma protein targets linking menopause timing to tau pathology.
  • To explore sex-specific associations between menopause, tau biomarkers, and proteins.
  • To understand the role of female biology in Alzheimer's disease.

Main Methods:

  • Plasma proteomics analyzed 132 proteins in postmenopausal women and men.
  • Correlations screened associations between age at menopause and protein levels.
  • Mediation analyses tested protein roles in linking menopause age and tau biomarkers.

Main Results:

  • Seventeen proteins associated with menopause age, including immune, metabolic, and synaptic markers.
  • Eleven proteins correlated with both menopause age and key tau biomarkers (ptau181, ptau231, MAPT).
  • AGRN mediated the relationship between menopause age and tau measures; several proteins showed stronger associations in females.

Conclusions:

  • Menopause timing is associated with biological factors relevant to brain aging, especially immune and tau biology.
  • AGRN is a key candidate linking menopause and tau pathology, potentially explaining female AD vulnerability.
  • Leveraging female-specific biology offers new avenues for understanding tau pathology and AD.