Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease
Open accessAbstract
Over 90% of patients with Alzheimer's disease (AD) develop cerebral amyloid angiopathy (CAA). Severe dyshoric CAA, in which amyloid extends into the surrounding brain parenchyma, may be associated with adjacent clustering of tau‐immunopositive neurites but the relationship of CAA to neurofibrillary pathology has not been systematically investigated. In the present study this relationship was examined in sections of frontal, temporal and parietal cortex from 25 AD patients with moderate to severe CAA and 26 with mild or absent CAA. We measured immunolabelling of abnormally phosphorylated tau adjacent to Aβ‐laden and non‐Aβ‐laden arteries and arterioles, and in cortex away from arteries and arterioles. We also analysed the possible influence of APOE genotype on these measurements. There were no significant differences between the lobes in measurements of tau labelling, either around blood vessels or elsewhere in the cortex. However, tau labelling around Aβ‐laden arteries and arterioles significantly exceeded that around non‐Aβ‐laden blood vessels (P < 0.001) and this, in turn was greater than the labelling of cortex away from blood vessels (P < 0.001). There was no association between APOE ɛ4 and the immunolabelling density for tau, whether around amyloid‐ or non‐amyloid‐laden arteries and arterioles, or in the cerebral cortex away from these. We propose that both CAA and peri‐vascular accumulation of hyperphosphorylated tau may be a consequence of elevated levels of soluble Aβ around cortical arteries and arterioles.
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An association between parenchymal CAA pathology, perivascular tau pathology, and neuronal tau pathology severity has been described.
“Moreover, an association between parenchymal CAA pathology, perivascular tau pathology [36], and neuronal tau pathology severity has been described [27]”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [36]
ApoE has a relevant role in AD pathophysiology in astrocytes and immune response to the disease.
“It is known that ApoE has a relevant role in AD pathophysiology in astrocytes and immune response to the disease [35, 36].”
From Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer’s dementia (2022) · cites this paper as [36]
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“It is known that ApoE has a relevant role in AD pathophysiology in astrocytes and immune response to the disease [35, 36].”
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Vascular Lesions, <i>APOE</i> ε4, and Tau Pathology in Alzheimer Disease
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- Authors
- Williams, S., Chalmers, K., Wilcock, G. K., & Love, S.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Love, S.
- ORCID
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2005-05-25
- Volume
- 31
- Issue
- 4
- Pages
- 414-421
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W2142812465
- Cited by
- 49
- References
- 26
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 5 · 2014: 1 · 2012: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- green
- eprints.uwe.ac.uk
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- UWE Research Repository (UWE Bristol) (submittedVersion, cc-by)
- Funders
- Chinese Academy of Agricultural Sciences
- 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, neurofibrillary pathology, hyperphosphorylated tau, amyloid-beta, APOE ε4
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Arteries, Arterioles, Brain, Female, Genotype, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Male, Middle Aged, Phosphorylation, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Neurofibrillary Tangles, tau Proteins
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