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Basic Science and Pathogenesis.

Elizabeth Ochoa1, Savannah Barannikov1, Mallory Keating2

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|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Hispanic individuals face higher dementia risk. This study analyzed gene expression in their brains, finding unique patterns in Alzheimer's disease (AD) and cerebrovascular disease (CVD) that may inform precision medicine.

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Area of Science:

  • Neuroscience
  • Genetics
  • Pathology

Background:

  • Hispanic individuals have a 1.5x higher risk of Alzheimer's disease and related dementias but are underrepresented in research.
  • Previous studies suggest altered Alzheimer's pathology burden and ancestry-related gene expression modification in Hispanic populations.
  • Few studies have investigated differential gene expression in dementia using postmortem brain tissue from Hispanic decedents.

Purpose of the Study:

  • To investigate neuroinflammatory gene expression in the postmortem brain tissue of Hispanic decedents with dementia.
  • To identify ancestry- and etiology-specific transcriptional profiles in dementia.
  • To lay the groundwork for precision medicine approaches in dementia care for at-risk, underrepresented populations.

Main Methods:

  • RNA was extracted from the frontal cortex of postmortem brain tissue from Hispanic and non-Hispanic decedents with Alzheimer's disease (AD), cerebrovascular disease (CVD), or mixed etiology (ADCVD).
  • Gene expression was quantified using the NanoString Human Neuroinflammation panel and SPRINT nCounter technology.
  • Analysis followed NanoString Advanced Analysis criteria, with low count and background genes excluded.

Main Results:

  • A shared pathway enrichment of the Astrocyte Function gene set was observed when comparing Hispanic decedents with AD or ADCVD to non-Hispanic decedents.
  • Two genes were differentially expressed in Hispanic AD and seven in Hispanic ADCVD compared to non-Hispanic decedents.
  • Genes P2RY12, NRP2, and PRKACB, among others, showed increased transcript levels in the frontal cortex of Hispanic decedents with CVD compared to other etiologies.

Conclusions:

  • Preliminary findings suggest distinct transcriptional profiles in cerebrovascular disease (CVD) influenced by ancestry and etiology.
  • Ancestry appears to modify a limited number of genes in Alzheimer's disease (AD) and mixed etiology dementia (ADCVD).
  • Further research will examine differential gene expression relative to pathology and develop functional genetic models to identify Hispanic ancestry- and disease-specific genes for precision dementia care.