Two Types of Sporadic Cerebral Amyloid Angiopathy
Abstract
Cerebral amyloid angiopathy (CAA) is a type of beta-amyloidosis that occurs in leptomeningeal and cortical vessels of the elderly. In a sample of 41 CAA cases including 16 Alzheimer disease (AD) cases and 28 controls, we show that 2 types of sporadic CAA exist: The first type is characterized by immunohistochemically detectable amyloid beta-protein (Abeta) in cortical capillaries, leptomeningeal and cortical arteries, arterioles, veins, and venules. It is referred to here as CAA-Type 1. The second type of CAA also exhibits immunohistochemically detectable Abeta deposits in leptomeningeal and cortical vessels, with the exception of cortical capillaries. This type is termed CAA-Type 2. In cases with CAA-Type 1, the frequency of the apolipoprotein E (ApoE) epsilon4 allele is more than 4 times greater than in CAA-Type 2 cases and in controls. CAA-Type 2 cases have a higher epsilon2 allele frequency than CAA-Type 1 cases and controls. The ratio of CAA-Type 2 to CAA-Type 1 cases does not shift significantly with respect to the severity of AD-related beta-amyloidosis, with respect to degrees of CAA-severity, or with increasing age. Therefore, CAA-Type 1 is unlikely to be the late stage of CAA-Type 2; rather, they represent 2 different entities. Since both the ApoE epsilon2 and the epsilon4 allele are known to be risk factors for CAA, we can assign the risk factor ApoE epsilon4 to a distinct morphological type of CAA. The ApoE epsilon4 allele constitutes a risk factor for CAA-Type 1…
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Type 2 cerebral amyloid angiopathy affects arterioles and small arteries, but not capillaries, and is 2-times more likely to be associated with APOE2.
“Type 2 CAA affects arterioles and small arteries, but not capillaries and is 2-times more likely to associated with APOE2 [47, 48].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [47]
Type 1 cerebral amyloid angiopathy affects capillaries, arterioles and small arteries and is 4-times more likely to be associated with APOE4.
“Type 1 CAA affects capillaries, arterioles and small arteries and it is 4-times more likely to be associated with APOE4.”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [47]
The largest percentage of AD patients with both CAA and CCA was found among ε4 allele carriers, while CAA without CCA was more frequent among ε2 and ε3 carriers.
“The largest percentage of AD patients with both CAA and CCA was found among ε4 allele carriers, while CAA without CCA was more frequent among ε2 and ε3 carriers [40, 42].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [40]
In these studies ε3 allele carriers and in particular ε3 allele homozygotes constituted the largest percentage among CAA/CCA free cases.
“In these studies ε3 allele carriers and in particular ε3 allele homozygotes constituted the largest percentage among CAA/CCA free cases.”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [40]
Both CAA and CCA variants of VAβ pathology have been described in AD autopsies and their relative preponderance has been linked to various APOE genotypes.
“Both CAA and CCA variants of VAβ pathology have been described in AD autopsies and their relative preponderance has been linked to various APOE genotypes [40–43].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [40]
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- Authors
- Thal, D. R., Ghebremedhin, E., Rüb, U., Yamaguchi, H., Del Tredici, K., & Braak, H.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Thal, Dietmar Rudolf
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-03
- Volume
- 61
- Issue
- 3
- Pages
- 282-293
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W2463189234
- Cited by
- 446
- References
- 7
- Citations by year
- 2026: 26 · 2025: 37 · 2024: 46 · 2023: 19 · 2022: 43 · 2021: 37 · 2020: 33 · 2019: 15 · 2018: 24 · 2017: 18 · 2016: 13 · 2015: 16 · 2014: 21 · 2013: 14 · 2012: 11
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Agricultural Sciences
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Keywords
- cerebral amyloid angiopathy, sporadic cerebral amyloid angiopathy, amyloid-beta deposition, APOE ε4, Alzheimer's disease, vascular amyloid, leptomeningeal vessels, immunohistochemistry, risk factors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Alleles, Alzheimer Disease, Amyloidosis, Apolipoproteins E, Blood Vessels, Brain Diseases, Capillaries, Cerebral Infarction, Cerebrovascular Circulation, Female, Gene Frequency, Genotype, Humans, Male, Middle Aged, Reference Values, Severity of Illness Index, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Genetic Predisposition to Disease
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