Relationships in Alzheimer's disease between the extent of Aβ deposition in cerebral blood vessel walls, as cerebral amyloid angiopathy, and the amount of cerebrovascular smooth muscle cells and collagen
Abstract
The relationship between degree of cerebral amyloid angiopathy (CAA) and the amount of smooth muscle cells (SMCs) and deposition of collagen IV fibres (COL IV) was investigated in the frontal and occipital cortex of 70 patients with autopsy confirmed Alzheimer's disease (AD). The extent of CAA was significantly greater in occipital than in frontal cortex, although SMC loss was greater in frontal than in occipital cortex. COL IV staining was significantly higher in occipital than in frontal cortex. The degree of SMC loss correlated with CAA, as Aβ 40 but not as Aβ 42 or total Aβ, in frontal cortex, but not in occipital cortex. Leptomeningeal arteries within occipital cortex showed significantly greater external diameter, greater wall thickness and greater luminal area than those in frontal cortex. The degree of CAA correlated with thickness of blood vessel wall and external diameter in frontal cortex, whereas extent of SMC loss correlated with thickness of blood vessel wall in occipital cortex. There were significant negative correlations between duration of disease and thickness of vessel wall, external diameter and luminal area. In patients with disease durations exceeding 10 years, external vessel diameter and thickness of the vessel wall were both halved compared with patients with durations less than 5 years; luminal area was reduced by about 75%. Blood vessels in AD undergo degenerative changes involving deposition of Aβ and COL IV with loss of SMC. SMC loss may relate to increasing Aβ deposition in early stages of disease, but this relationship may be lost with disease progression.
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Thio-S positive blood vessel diameter was increased in microglia-depleted 5xFAD mice.
“Immunolabeling for the endothelial tight junction marker, Claudin-5, revealed an increase in Thio-S positive blood vessel diameter (Supplementary Figure 7I–K), consistent with prior data26, and reduced intensity of Claudin-5 staining in Aβ-associated blood vessels (Supplementary Figure 7L), suggesting impaired vascular integrity in the presence of Aβ pathology.”
From Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model (2019) · cites this paper as [26]
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Self-citation
- Authors
- Tian, J., Shi, J., Smallman, R., Iwatsubo, T., & Mann, D. M. A.
- Affiliations
- Beijing University of Chinese Medicine (CN)
- University of Manchester (GB)
- The University of Tokyo (JP)
- Corresponding author
- Mann, D. M. A.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2006-04-25
- Volume
- 32
- Issue
- 3
- Pages
- 332-340
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2156619251
- Cited by
- 61
- References
- 36
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 6 · 2012: 4
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, cerebral amyloid angiopathy, amyloid-beta deposition, smooth muscle cells, type IV collagen, vessel wall thickness, leptomeningeal arteries, frontal cortex, occipital cortex, disease duration, luminal area
- MeSH terms
- Aged, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Middle Aged, Muscle, Smooth, Vascular, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Collagen Type IV, Myocytes, Smooth Muscle
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