Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions
Open accessAbstract
White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.
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The majority of published studies have emphasized the spatial heterogeneity of WMHs but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.
“The majority of published studies have emphasized the spatial heterogeneity of WMHs [25,26], but have left the potential heterogeneous influences of regional Aβ deposition relatively unexplored.”
From Amyloid-PET and White Matter Hyperintensities Have Independent Effects on Baseline Cognitive Function and Synergistic Effects on Longitudinal Executive Function (2023) · cites this paper as [26]
The Introduction describes prior studies of differing WMH locations across conditions, supporting the citation’s point that spatial heterogeneity has received attention. It does not establish that a majority of published studies emphasized this topic. Its discussion of limited amyloid-related research concerns overall amyloid burden and WMH location, not specifically the heterogeneous influences of regional Aβ deposition. (LLM, conf=0.82)
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- Authors
- Weaver, N. A., Doeven, T., Barkhof, F., Biesbroek, J. M., Groeneveld, O. N., Kuijf, H. J., Prins, N. D., Scheltens, P., Teunissen, C. E., van der Flier, W. M., & Biessels, G. J.
- Affiliations
- University Medical Center Utrecht (NL)
- Amsterdam Neuroscience (NL)
- Corresponding author
- Weaver, Nick A.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 84
- Pages
- 225-234
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2967452790
- Cited by
- 71
- References
- 65
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 15 · 2023: 17 · 2022: 8 · 2021: 7 · 2020: 6
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Hartstichting
- ZonMw
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- white matter hyperintensities, amyloid-beta 42, phosphorylated tau, splenium of corpus callosum, posterior thalamic radiation, periventricular lesions, cerebral small vessel disease, Alzheimer's disease, lesion mapping, memory clinic patients
- MeSH terms
- Alzheimer Disease, Humans, Magnetic Resonance Imaging, Peptide Fragments, Amyloid beta-Peptides, tau Proteins, White Matter
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