Journal
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
Volume 40, Issue 3, Pages 284-295Publisher
WILEY
DOI: 10.1111/nan.12085
Keywords
Alzheimer's disease; hippocampus; microvessel; post-stroke dementia; stroke; vascular dementia
Categories
Funding
- Newcastle Centre for Brain Ageing and Vitality (BBSRC)
- Newcastle Centre for Brain Ageing and Vitality (EPSRC)
- Newcastle Centre for Brain Ageing and Vitality (ESRC)
- Newcastle Centre for Brain Ageing and Vitality (MRC)
- Newcastle Centre for Brain Ageing and Vitality (LLHW)
- UK Medical Research Council (MRC) [G0500247]
- Alzheimer's Research UK (UK)
- UK MRC [G0400074]
- Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases
- Alzheimer's Society
- Alzheimer's Research UK (ARUK)
- MRC [G0700718, G0900652, G0502157, G0400074, G1100540, MR/L016451/1, G0500247] Funding Source: UKRI
- Alzheimers Research UK [ART-PhD2009-2] Funding Source: researchfish
- Medical Research Council [MR/L016451/1, G0900652, G0502157, G0400074, G0500247, G0700718B, G0700718, G1100540] Funding Source: researchfish
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BackgroundOptimal vascular function is vital for prevention of dementia. We hypothesized that elderly post-stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia. MethodsUsing stereological spherical probe software, we compared the length density (Lv, cumulative vessel length per unit tissue volume) of hippocampal microvessels in post mortem brain tissue from post-stroke survivors, Alzheimer's disease (AD), vascular dementia (VaD) and normal ageing control subjects. We also assessed microvessel diameters in the same subjects. Microvessels were identified by markers of endothelial cells (glucose transporter 1; GLUT1), basement membrane (collagen IV; COL4) and smooth muscle cell -actin (SMA). ResultsWe found increased Lv of both GLUT1 and COL4 immunostained microvessels (P<0.05) in the hippocampal CA1 region of post-stroke demented (PSD) and AD cases compared with post-stroke nondemented (PSND), control and VaD subjects. However, no changes were apparent in the CA2 region. We also noted significant increase in Lv in the entorhinal cortex of AD compared with PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared with PSND, as well as in AD and VaD compared with controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12m. ConclusionsAn increase in microvascular Lv in AD and PSD suggests either an increase in angiogenesis or the formation of newer microvessel loops in response to cerebral hypoperfusion. The decreased vessel diameters found in AD and VaD suggests increased vasoconstriction in dementia.
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