We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dysregulation of the renin‐angiotensin system in vascular dementia.
- Authors
Tayler, H. M.; Skrobot, O. A.; Baron, D. H.; Kehoe, P. G.; Miners, J. S.
- Abstract
The renin‐angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS signalling in white matter underlying the frontal and occipital cortex in neuropathologically confirmed cases of vascular dementia (n = 42), Alzheimer's disease (n = 50), mixed AD/VaD (n = 50) and age‐matched controls (n = 50). All cases were stratified according to small vessel disease (SVD) severity across both regions. ACE‐1 and ACE‐2 protein and activity was measured by ELISA and fluorogenic peptide assays respectively, and angiotensin peptide (Ang‐II, Ang‐III and Ang‐(1–7)) levels were measured by ELISA. ACE‐1 protein level and enzyme activity, and Ang‐II and Ang‐III, were elevated in the white matter in vascular dementia in relation to SVD severity. ACE‐1 and Ang‐II protein levels were inversely related to MAG:PLP1 ratio, a biochemical marker of brain tissue oxygenation that when reduced indicates cerebral hypoperfusion, in a subset of cases. ACE‐2 level was elevated in frontal white matter in vascular dementia. Ang‐(1–7) level was elevated across all dementia groups compared to age‐matched controls but was not related to SVD severity. RAS signalling was not altered in the white matter in Alzheimer's disease. In the overlying frontal cortex, ACE‐1 protein was reduced and ACE‐2 protein increased in vascular dementia, whereas angiotensin peptide levels were unchanged. These data indicate that RAS signalling is dysregulated in the white matter in vascular dementia and may contribute to the pathogenesis of small vessel disease.
- Subjects
VASCULAR dementia; CARDIOVASCULAR system; RENIN-angiotensin system; ALZHEIMER'S disease; CEREBRAL circulation; ANGIOTENSIN II
- Publication
Brain Pathology, 2024, Vol 34, Issue 4, p1
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/bpa.13251