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Basic Science and Pathogenesis

Hsin-Pei Wang1, Naomi Saito2, Laurel Beckett2

  • 1University of California, Davis, Sacramento, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed

Insights

Cardiovascular risk factors like diabetes and hypercholesterolemia are linked to Alzheimer disease (AD) neuropathology, including neuropil threads and amyloid angiopathy. This highlights the need for diverse cohorts in AD research.

Area of Science:

  • Neuropathology
  • Neuroscience
  • Cardiovascular Disease Research

Background:

  • Cardiovascular risk factors are linked to Alzheimer disease (AD) progression and neuropathology.
  • Their specific impact on regional brain pathology in diverse populations is understudied.

Purpose of the Study:

  • To examine the relationship between diabetes, hypertension, hypercholesterolemia, and neuropathologies in a diverse cohort of individuals with Alzheimer disease.
  • To investigate regional differences in arteriolosclerosis, cerebral amyloid angiopathy (CAA), core plaques (CPs), diffuse plaques (DPs), and neuropil threads (NTs).

Main Methods:

  • A cohort study of 276 Hispanic and non-Hispanic White decedents with pathologically confirmed Intermediate/High AD.
  • Assessed three-level categorizations (absent, active/recent, inactive/remote) of diabetes, hypertension, and hypercholesterolemia.
  • Used semi-quantitative assessments for regional neuropathologies adapting CERAD criteria.

Main Results:

  • Active diabetes associated with increased frontal neuropil threads (NTs).
  • Active hypercholesterolemia correlated with greater temporal cortex cerebral amyloid angiopathy (CAA) and temporal core plaques (CPs).
  • No significant associations found between hypertension and neuropathology.

Conclusions:

  • Diverse cohorts are crucial for generalizable Alzheimer disease (AD) research.
  • Established links between cardiovascular risk factors and AD neuropathologies support precision medicine for dementia.
Abstract

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