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Cardiac biomarkers are enzymes, proteins, and hormones released into the blood when cardiac cells are injured. They are powerful tools for triaging.
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Biomarkers.

Yifan Zhao1, Tao Jin1, Nicholas F Fitz2

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

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary

Alzheimer's disease impacts brain blood flow and glucose metabolism differently in males and females. This study reveals sex-specific changes in neurovascular and metabolic pathways during aging in preclinical models.

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Genomics

Background:

  • Alzheimer's disease (AD) involves neurodegeneration and glial cell activation.
  • Vascular factors like cerebral amyloid angiopathy (CAA) are common in AD but present differently between sexes.
  • Sex-specific pathways in AD pathogenesis are not fully understood.

Purpose of the Study:

  • To investigate sex-specific differences in neurovascular and metabolic resilience in Alzheimer's disease.
  • To correlate functional brain imaging with single-cell transcriptomics in preclinical AD models.
  • To elucidate cell-specific molecular pathways underlying sex differences in AD.

Main Methods:

  • Utilized APP/PS1 transgenic mice and B6C3 controls across lifespan (4-24 months).
  • Employed quantitative cerebral blood flow (qCBF) and chemical exchange saturation transfer (CEST) MRI at 9.4T for vascular and metabolic assessment.
  • Conducted single-cell mRNA sequencing on microglia and astrocytes, alongside histological analysis of amyloid plaques and CAA.

Main Results:

  • Control mice exhibited higher cerebral blood flow (CBF) and glucose uptake than AD mice.
  • Sex-specific differences were observed: male controls had higher CBF than females, a difference lost in AD.
  • AD females showed reduced glucose metabolism compared to control females, while AD males had lower amide and creatine levels than AD males.

Conclusions:

  • Presented an integrated view of vascular and neuroenergetic function in preclinical AD.
  • Demonstrated the utility of combining multiscale imaging and transcriptomics for studying sex-specific brain aging.
  • Highlighted distinct trajectories of healthy and pathological brain aging influenced by sex.