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Cited by 161Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCerebrovascular and genetic disorders

Cortical tau load is associated with white matter hyperintensities

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McAleese, Kirsty E., Firbank, Michael, Dey, Madhurima, Colloby, Sean J., Walker, Lauren, Johnson, Mary, Beverley, Joshua R., Taylor, John Paul +3 more·2015·Acta Neuropathologica Communications
DOI 10.1186/s40478-015-0240-0PMC PMC4589169
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Abstract

INTRODUCTION: Cerebral white matter lesions (WML), visualized as white matter hyperintensities (WMH) on T2-weighted MRI, encompass structural damage and loss of integrity of the cerebral white matter (WM) and are commonly assumed to be associated with small vessel disease (SVD). However, it has been suggested that WM damage may also be the result of degenerative axonal loss that is secondary to cortical Alzheimer's disease (AD) pathologies i.e., hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ). Here we investigate the influence of HPτ, Aβ and SVD on WMH severity. RESULTS: 36 human post-mortem right fixed cerebral hemispheres (mean age 84.4 ± 7.7 years; male: 16, female: 20) containing varying amounts of AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI with WMH assessed according to the age related white matter change scale (ARWMC). After dissection, using tissue samples from the frontal, temporal, parietal and occipital regions from the right hemisphere, we quantitatively assessed cortical HPτ and Aβ pathology burden by measuring the percentage area covered by AT8 immunoreactivity (HPτ-IR) and 4G8 immunoreactivity (Aβ-IR), and assessed the severity of WM SVD by calculating the sclerotic index (SI) of WM arteries/arterioles. HPτ-IR, Aβ-IR, and SI were compared with ARWMC scores. HPτ-IR, Aβ-IR and WM ARWMC scores were all significantly higher in AD cases compared to controls, while SI values were similar between groups. ARWMC scores correlated with HPτ-IR, Aβ-IR and SI in various regions, however, linear regression revealed that only HPτ-IR was a significant independent predictor of ARWMC scores. CONCLUSIONS: Here we have shown that increasing cortical HPτ burden independently predicted the severity of WMH indicating its potentially important role in the pathogenesis of WM damage. Moreover, our findings suggest that in AD patients the presence of WMH may indicate cortical AD-associated pathology rather than SVD. Further studies are warranted to elucidate the pathological processes that lead to WM damage and to clarify if WMH may serve as a general biomarker for cortical AD-associated pathology.

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Authors
McAleese, K. E., Firbank, M., Dey, M., Colloby, S. J., Walker, L., Johnson, M., Beverley, J. R., Taylor, J. P., Thomas, A. J., O’Brien, J. T., & Attems, J.
Affiliations
Newcastle University (GB)
Corresponding author
McAleese, Kirsty E.
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2015-09-30
Volume
3
Issue
1
Pages
60-60
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-015-0240-0
PMC
PMC4589169
OpenAlex
W1834356056
Cited by
161
References
70
Citations by year
2026: 11 · 2025: 19 · 2024: 23 · 2023: 13 · 2022: 20 · 2021: 20 · 2020: 21 · 2019: 12 · 2018: 11 · 2017: 6 · 2016: 5
FWCI
5.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Alzheimer's Society UK
  • Dunhill Medical Trust (R173/1110)
  • UK Medical Research Council
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
Keywords
white matter hyperintensities, hyperphosphorylated tau, amyloid-beta, Alzheimer's disease, cerebral small vessel disease, cerebral white matter lesions, axonal loss, postmortem brain, T2-weighted MRI, biomarkers
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Female, Humans, Magnetic Resonance Imaging, Male, Postmortem Changes, Severity of Illness Index, Cohort Studies, Amyloid beta-Peptides, tau Proteins, Statistics, Nonparametric, Leukoencephalopathies

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