ArticleActa neuropathologica2017
Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.
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Who cites it
169 citing papers in PubMed, 1 synthesis or guideline pooled it, 275 citations in OpenAlex.
- DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and contributes to Alzheimer's disease and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Pooled it
- Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers: Post Hoc Secondary Analysis of the SPRINT MIND Randomized Clinical Trial.JAMA network open · 2023Trial
- Lesion-Level Subtypes of White Matter Hyperintensity Evolution Beyond Spatial Location.Neurology · 2026Observational
- Norms for Automatic Estimation of White Matter Hyperintensities Burden: LST-AI Service in neuGRID.Diagnostics (Basel, Switzerland) · 2026Article
- 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
- Article
- Regional growth rates of white matter hyperintensities are associated with beta-amyloid burden.Neurobiology of aging · 2026Article
- Characterizing spatiotemporal white matter hyperintensity pathophysiology in vivo to disentangle vascular and neurodegenerative contributions.Nature communications · 2026Article
- Progression of fiber bundle damage in amnestic Alzheimer's disease and LATE: a 2-year fixel-based study.GeroScience · 2026Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Sex differences in diffusion-weighted imaging outcomes in autosomal dominant Alzheimer's disease.Brain communications · 2026Article
- Amyloid and tau pathologies are drivers of white matter damage in aging and Alzheimer's disease.medRxiv : the preprint server for health sciences · 2025Article
- Vascular risk factors mediate the relationship between education and white matter hyperintensities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Heterogeneity of white matter hyperintensities in Alzheimer's disease captured by multimodal neuroimaging.Scientific reports · 2025Article
- The role of Tau, amyloid-β and neuroinflammation in the association between cognition and white matter hyperintensities in a southeast Asian cohort.The journal of prevention of Alzheimer's disease · 2025Article
- White matter microstructure is differentially impacted by cerebral amyloid angiopathy, neurofibrillary tangles, and neuritic plaque co-pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Biomarker Profile of Alzheimer's Disease for Disease-Modifying Treatment Eligibility: Questions and Debates.International journal of molecular sciences · 2025Review
- Pathologic and Therapeutic Schwann Cells.Cells · 2025Review
- White matter hyperintensities and their impact in brain structure and function in alzheimer's disease and behavioral variant frontotemporal dementia across Latin America and the United States: a cross-sectional study.Alzheimer's research & therapy · 2025Article
- Comorbid Pathologies and Their Impact on Dementia with Lewy Bodies-Current View.International journal of molecular sciences · 2025Review
109 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups. We investigated differences in the composition and aetiology of parietal WML from AD and non-demented controls. Parietal WML tissue from 55 human post-mortem brains (AD, n = 27; non-demented controls, n = 28) were quantitatively assessed for axonal loss and demyelination, as well as for cortical HPτ and Aβ burden and SVD. Biochemical assessment included Wallerian degeneration protease calpain and the myelin-associated glycoprotein (MAG) to proteolipid protein (PLP) ratio (MAG:PLP) as a measure of hypoperfusion. WML severity was associated with both axonal loss and demyelination in AD, but only with demyelination in controls. Calpain was significantly increased in WML tissue in AD, whereas MAG:PLP was significantly reduced in controls. Calpain levels were associated with increasing amounts of cortical AD-pathology but not SVD. We conclude that parietal WML seen in AD differ in their pathological composition and aetiology compared to WML seen in aged controls: WML seen in AD may be associated with Wallerian degeneration that is triggered by cortical AD-pathology, whereas WML in aged controls are due to ischaemia. Hence, parietal WML as seen on MRI should not invariably be interpreted as a surrogate biomarker for SVD as they may be indicative of cortical AD-pathology, and therefore, AD should also be considered as the main underlying cause for cognitive impairment in cases with parietal WML.
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Registered trials
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