The association between white matter hyperintensities and amyloid and tau deposition
Open accessAbstract
White matter hyperintensities (WMHs) frequently occur in Alzheimer's Disease (AD) and have a contribution from ischemia, though their relationship with β-amyloid and cardiovascular risk factors (CVRFs) is not completely understood. We used AT classification to categorize individuals based on their β-amyloid and tau pathologies, then assessed the effects of β-amyloid and tau on WMH volume and number. We then determined regions in which β-amyloid and WMH accumulation were related. Last, we analyzed the effects of various CVRFs on WMHs. As secondary analyses, we observed effects of age and sex differences, atrophy, cognitive scores, and APOE genotype. PET, MRI, FLAIR, demographic, and cardiovascular health data was collected from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3) (N = 287, 48 % male). Participants were categorized as A + and T + if their Florbetapir SUVR and Flortaucipir SUVR were above 0.79 and 1.25, respectively. WMHs were mapped on MRI using a deep convolutional neural network (Sepehrband et al., 2020). CVRF scores were based on history of hypertension, systolic and diastolic blood pressure, pulse rate, respiration rate, BMI, and a cumulative score with 6 being the maximum score. Regression models and Pearson correlations were used to test associations and correlations between variables, respectively, with age, sex, years of education, and scanner manufacturer as covariates of no interest. WMH volume percent was significantly associated with global β-amyloid (r = 0.28, p < 0.001), but not tau (r = 0.05, p = 0.25). WMH volume percent was higher in individuals with either A + or T + pathology compared to controls, particularly within in the A+/T + group (p = 0.007, Cohen's d = 0.4, t = -2.5). Individual CVRFs nor cumulative CVRF scores were associated with increased WMH volume. Finally, the regions where β-amyloid and WMH count were most positively associated were the middle temporal region in the right hemisphere (r = 0.18, p = 0.002) and the fusiform region in the left hemisphere (r = 0.017, p = 0.005). β-amyloid and WMH have a clear association, though the mechanism facilitating this association is still not fully understood. The associations found between β-amyloid and WMH burden emphasizes the relationship between β-amyloid and vascular lesion formation while factors like CVRFs, age, and sex affect AD development through various mechanisms. These findings highlight potential causes and mechanisms of AD as targets for future preventions and treatments. Going forward, a larger emphasis may be placed on β-amyloid's vascular effects and the implications of impaired brain clearance in AD.
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Most cross-sectional studies reported an association between WMH and amyloid markers (CSF Aβ42 or Aβ PET) but not tau markers.
“Most cross‐sectional studies reported an association between WMH and amyloid markers (either CSF Aβ42 or Aβ deposition on PET) but not tau markers. 55 , 56 , 57 , 58 , 59”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [56]
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КОГНИТИВНЫЕ НАРУШЕНИЯ ПРИ МЕТАБОЛИЧЕСКОМ СИНДРОМЕ (обзор литературы)
Иванова, А. А., Смирнова, А. А., Тайгибова, А. Ю., Софиева, Г. Э., Гагулина, О. М., Михалёв, П. А., & Раевский, К. П. (2025) · Успехи геронтологии · doi:10.34922/ae.2025.38.4.005
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- Authors
- Alban, S. L., Lynch, K. M., Ringman, J. M., Toga, A. W., Chui, H. C., Sepehrband, F., & Choupan, J.
- Affiliations
- University of Southern California (US)
- ORCID
- Venue
- NeuroImage: Clinical
- Publisher
- Elsevier BV
- Published
- 2023
- Volume
- 38
- Pages
- 103383
- ISSN
- 2213-1582 (ISSN-L)
- PMC
- PMC10060905
- OpenAlex
- W4327921944
- Cited by
- 35
- References
- 115
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 10 · 2023: 3
- FWCI
- 7.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage Clinical (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Defense (W81XWH-12-2-0012)
- National Institutes of Health (1P30AG066530-01, USC ADRC 5P50AG005142, 2P41EB015922-21,1P01AG052350-01, U01AG024904)
- Alzheimer's Drug Discovery Foundation
- National Institute on Aging (R01AG070825, RF1MH123223, T32AG058507)
- AbbVie
- Alzheimer's Disease Neuroimaging Initiative
- Alzheimer's Association
- National Institute of Mental Health
- National Institute of Biomedical Imaging and Bioengineering
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- white matter hyperintensities, amyloid-beta, tau protein, Alzheimer's disease, cardiovascular risk factors, amyloid PET, florbetapir, flortaucipir, deep convolutional neural networks, middle temporal cortex, fusiform cortex, APOE genotype, brain atrophy, ischemia, sex differences, age differences, cognitive test scores, white matter
- MeSH terms
- Alzheimer Disease, Amyloid, Female, Humans, Male, Amyloid beta-Peptides, tau Proteins, Amyloidogenic Proteins, Cognitive Dysfunction, White Matter
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