White matter capillaries in vascular and neurodegenerative dementias
Abstract 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 d...
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40478-019-0666-x |
| _version_ | 1818837149560078336 |
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| author | Yoshiki Hase Ren Ding Gina Harrison Emily Hawthorne Amilia King Sean Gettings Charlotte Platten William Stevenson Lucinda J. L. Craggs Raj N. Kalaria |
| author_facet | Yoshiki Hase Ren Ding Gina Harrison Emily Hawthorne Amilia King Sean Gettings Charlotte Platten William Stevenson Lucinda J. L. Craggs Raj N. Kalaria |
| author_sort | Yoshiki Hase |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-19T03:17:55Z |
| format | Article |
| id | doaj.art-538e8d54f1e6478297e29e0744d820e8 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-12-19T03:17:55Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-538e8d54f1e6478297e29e0744d820e82022-12-21T20:37:50ZengBMCActa Neuropathologica Communications2051-59602019-02-017111210.1186/s40478-019-0666-xWhite matter capillaries in vascular and neurodegenerative dementiasYoshiki Hase0Ren Ding1Gina Harrison2Emily Hawthorne3Amilia King4Sean Gettings5Charlotte Platten6William Stevenson7Lucinda J. L. Craggs8Raj N. Kalaria9Neurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityNeurovascular Research Group, Institute of Neuroscience, Newcastle University, Campus for Ageing and VitalityAbstract 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.http://link.springer.com/article/10.1186/s40478-019-0666-xAlzheimer’s diseaseDementiaDementia with Lewy bodiesMicrovascular pathologyMixed dementiaParkinson’s disease with dementia |
| spellingShingle | Yoshiki Hase Ren Ding Gina Harrison Emily Hawthorne Amilia King Sean Gettings Charlotte Platten William Stevenson Lucinda J. L. Craggs Raj N. Kalaria White matter capillaries in vascular and neurodegenerative dementias Acta Neuropathologica Communications Alzheimer’s disease Dementia Dementia with Lewy bodies Microvascular pathology Mixed dementia Parkinson’s disease with dementia |
| title | White matter capillaries in vascular and neurodegenerative dementias |
| title_full | White matter capillaries in vascular and neurodegenerative dementias |
| title_fullStr | White matter capillaries in vascular and neurodegenerative dementias |
| title_full_unstemmed | White matter capillaries in vascular and neurodegenerative dementias |
| title_short | White matter capillaries in vascular and neurodegenerative dementias |
| title_sort | white matter capillaries in vascular and neurodegenerative dementias |
| topic | Alzheimer’s disease Dementia Dementia with Lewy bodies Microvascular pathology Mixed dementia Parkinson’s disease with dementia |
| url | http://link.springer.com/article/10.1186/s40478-019-0666-x |
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