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Updated: Jun 27, 2026

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White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel

Lisa C Silbert1,2, Natalie E Roese1, Victoria Krajbich3

  • 1National Institute on Aging, Layton Aging & Alzheimer's Disease Research Center, Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|April 17, 2024
PubMed
Abstract

Insights

Age-related white matter hyperintensities (WMHs) involve demyelination and altered astrocyte function, impacting water balance in the aging brain. These changes extend into normal-appearing white matter (NAWM) near WMHs.

Area of Science:

  • Neuroimaging and neuropathology
  • Aging and brain health
  • White matter diseases

Background:

  • Age-related white matter hyperintensities (WMHs) are common findings on MRI and linked to cognitive decline.
  • Understanding the cellular and molecular basis of WMHs and adjacent normal-appearing white matter (NAWM) is crucial for aging brain research.

Purpose of the Study:

  • To investigate the histopathological features of MRI-detected WMHs and surrounding NAWM.
  • To focus on astroglial phenotypes and aquaporin (AQP) expression in WMHs and NAWM.

Main Methods:

  • Utilized post mortem (PM) 7 tesla MRI on brain samples from 51 oldest old individuals.
  • Performed targeted histopathological sampling of WMHs and NAWM.
  • Digitized and quantified stained slides, analyzing molecular characteristics using mixed-effects models.

Main Results:

  • PM MRI-identified WMHs showed demyelination, microglial activation, and significant astrocytic alterations, including disrupted AQP expression.
  • Similar pathological changes were observed in the surrounding NAWM, decreasing in severity with distance from WMHs.
  • Decreased AQP1 and AQP4 expression was noted in WMHs and proximal NAWM, suggesting impaired water homeostasis.

Conclusions:

  • WMHs and associated NAWM pathology involve inflammation, demyelination, and gliosis.
  • Disrupted AQP expression in WMHs and NAWM indicates a failure in maintaining water homeostasis, contributing to brain damage in aging.
  • The findings highlight the widespread impact of WMH pathology on adjacent white matter structure and function.
Keywords:
aquaporinmagnetic resonance imagingoldest oldpathologywhite matter hyperintensity

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