ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 8 citations in OpenAlex.
- Altered T1w/T2w-FLAIR Ratio in White Matter Hyperintensities as an Indicator of Structural Integrity Loss: Association with Alzheimer's Disease and Vascular Dementia.medRxiv : the preprint server for health sciences · 2026Article
- Aging macaques bridge the translational gap in perivascular space biology.Scientific reports · 2026Article
- Aging-related lateral ventricular shape changes and corresponding mechanical loading derived from longitudinal image registration.Biomechanics and modeling in mechanobiology · 2026Article
- Short T1 Fraction as a Marker of Myelin Content: Evidence from Postmortem MRI and Histology.bioRxiv : the preprint server for biology · 2026Article
- Perilesional white matter gradients reveal microstructural differences in cerebral amyloid angiopathy versus Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Aging macaques bridge the translational gap in perivascular space biology.bioRxiv : the preprint server for biology · 2026Article
- The 2024 NIA-AA biological definition of Alzheimer's disease: linking biomarkers to clinical practice.Frontiers in dementia · 2026Review
- Free Water-Corrected Fractional Anisotropy in Normal-Appearing White Matter as a Potential Neuroimaging Biomarker for Attention and Executive Function Impairment in Cerebral Small Vessel Disease.CNS neuroscience & therapeutics · 2025Article
- Operationalizing postmortem pathology-MRI association studies in Alzheimer's disease and related disorders with MRI-guided histology sampling.Acta neuropathologica communications · 2025Article
- White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
introductionAge-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes.
methodsBrain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM. Stained slides were digitized and quantified. Mixed-effects models determined differences in molecular characteristics between WMHs and the NAWM and across NAWM.
resultsPM MRI-targeted WMHs are characterized by demyelination, microglial activation, and prominent astrocytic alterations, including disrupted aquaporin (AQP) expression. Similar changes occur within the surrounding NAWM in a pattern of decreasing severity with increased distance from WMHs. DISCUSSION: Decreased AQP expression within WMH and proximal NAWM suggest an overwhelmed system wherein water homeostasis is no longer maintained, contributing to WM damage in older individuals. HIGHLIGHTS: Post mortem magnetic resonance imaging (MRI) was used to characterize the pathology of white matter hyperintensities (WMHs) and surrounding normal appearing white matter (NAWM). Stained immunohistochemical (IHC) slides from targeted WMH and NAWM samples were digitized and quantified. WMHs and NAWM were associated with inflammation, demyelination, and gliosis. WMHs and NAWM astrocytic changes included decreased AQP1 and AQP4 expression. Abnormal NAWM pathology diminished in severity with increasing distance from WMH.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.