White matter capillaries in vascular and neurodegenerative dementias
Open accessAbstract
Previous studies suggest white matter (WM) integrity is vulnerable to chronic hypoperfusion during brain ageing. We assessed ~ 0.7 million capillary profiles in the frontal lobe WM across several dementias comprising Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease with dementia, vascular dementia, mixed dementias, post-stroke dementia as well as post-stroke no dementia and similar age ageing and young controls without significant brain pathology. Standard histopathological methods were used to determine microvascular pathology and capillary width and densities in 153 subjects using markers of the basement membrane (collagen IV; COL4) and endothelium (glucose transporter-1; GLUT-1). Variable microvascular pathology including coiled, tortuous, collapsed and degenerated capillaries as well as occasional microaneurysms was present in all dementias. As expected, WM microvascular densities were 20-49% lower than in the overlying cortex. This differential in density between WM and cortex was clearly demonstrated by COL4, which was highly correlated with GLUT-1 densities (Spearman's rho = 0.79, P = 0.000). WM COL4 immunopositive microvascular densities were decreased by ~ 18% across the neurodegenerative dementias. However, we found WM COL4 densities were increased by ~ 57% in post-stroke dementia versus ageing and young controls and other dementias. Using three different methods to measure capillary diameters, we found WM capillaries to be significantly wider by 19-45% compared to those in overlying neocortex apparent with both COL4 and GLUT-1. Remarkably, WM capillary widths were increased by ~ 20% across all dementias compared to ageing and young controls (P < 0.01). We also noted mean WM pathology scores incorporating myelin loss, arteriolosclerosis and perivascular spacing were correlated with COL4 immunopositive capillary widths (Pearson's r = 0.71, P = 0.032). Our key finding indicates that WM capillaries are wider compared to those in the overlying neocortex in controls but they dilate further during dementia pathogenesis. We suggest capillaries undergo restructuring in the deep WM in different dementias. This reflects compensatory changes to retain WM perfusion and integrity during hypoperfusive states in ageing-related dementias.
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The increase of radioligand binding in NAGM compared to NAWM may be attributed to the increased contribution of TSPO+ endothelial cells due to the reported increased vascularity of grey versus white matter.
“This may be attributed to the increased contribution of TSPO+ endothelial cells due to the reported increased vascularity of grey verses white matter (Hase et al., 2019).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Hase et al., 2019
We found an increase in endothelial contribution to TSPO expression relative to white matter as well as relative to grey matter lesions.
“However, as expected, we found an increase in endothelial contribution to TSPO expression relative to white matter as well as relative to grey matter lesions, which is consistent with the reported greater vascularity of grey verses white matter (Hase et al., 2019) and the hypo-cellularity of grey matter lesions (Bo, 2009).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Hase et al., 2019
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- Authors
- Hase, Y., Ding, R., Harrison, G., Hawthorne, E., King, A., Gettings, S., Platten, C., Stevenson, W., Craggs, L. J. L., & Kalaria, R. N.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Kalaria, Raj N.
- Venue
- Acta Neuropathologica Communications
- Published
- 2019-02-07
- Volume
- 7
- Issue
- 1
- Pages
- 16-16
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC6366070
- OpenAlex
- W2921621643
- Cited by
- 101
- References
- 35
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 25 · 2023: 15 · 2022: 9 · 2021: 14 · 2020: 16 · 2019: 5
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Alzheimer's Research UK (PG2013-022)
- Medical Research Council UK (G0500247)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- dementia, Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease dementia, vascular dementia, post-stroke dementia, microvascular pathology, type IV collagen, GLUT1, white matter perfusion, hypoperfusion, brain aging, arteriolosclerosis, demyelination, frontal lobe white matter
- MeSH terms
- Aged, Aged, 80 and over, Brain, Capillaries, Dementia, Female, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Microvessels, White Matter
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