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Morphometry of the hippocampal microvasculature in post-stroke and age-related dementias

Lookup NU author(s): Matthew Burke, Lucy Nelson, Janet Slade, Arthur Oakley, Dr Ahmad Khundakar, Professor Raj KalariaORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


BACKGROUND: Optimal vascular function is vital for prevention of dementia. We hypothesised that elderly post-stroke (PS) survivors who preserve cognitive function show unperturbed cerebral microvasculature compared to those who develop dementia.METHODS: Using 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 PS 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 α-actin (SMA).RESULTS: We 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 to post-stroke non-demented (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 to PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared to PSND, as well as in AD and VaD compared to controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12 μm.CONCLUSIONS: An 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.

Publication metadata

Author(s): Burke MJC, Nelson L, Slade JY, Oakley AE, Khundakar AA, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2014

Volume: 40

Issue: 3

Pages: 284-295

Print publication date: 01/04/2014

Online publication date: 13/03/2014

Acceptance date: 29/08/2013

Date deposited: 24/03/2014

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley-Blackwell


DOI: 10.1111/nan.12085

PubMed id: 24003901


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Funder referenceFunder name
Alzheimer's Research UK (ARUK)
Alzheimer's Society
Newcastle Centre for Brain Ageing and Vitality (BBSRC)
Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases
Alzheimer's Research UK (UK)
Newcastle Centre for Brain Ageing and Vitality (EPSRC)
Newcastle Centre for Brain Ageing and Vitality (ESRC)
Newcastle Centre for Brain Ageing and Vitality (LLHW)
Newcastle Centre for Brain Ageing and Vitality (MRC)
G0500247UK Medical Research Council (MRC)
G0400074UK MRC
G0700718Medical Research Council (MRC)