The DOI matches its Crossref record; 90 of the 90 references it cites were found in a registry or an index.
Capillary cerebral amyloid angiopathy identifies a distinct APOE ε4-associated subtype of sporadic Alzheimer’s disease
Abstract
The deposition of amyloid beta-protein (Abeta) in the vessel wall, i.e., cerebral amyloid angiopathy (CAA), is associated with Alzheimer's disease (AD). Two types of CAA can be differentiated by the presence or absence of capillary Abeta-deposits. In addition, as in Alzheimer's disease, risk for capillary CAA is associated with the apolipoprotein E (APOE) epsilon4-allele. Because these morphological and genetic differences between the two types of AD-related CAA exist, the question arises as to whether there exist further differences between AD cases with and without capillary CAA and, if so, whether capillary CAA can be employed to distinguish and define specific subtypes of AD. To address this question, we studied AD and control cases both with and without capillary CAA to identify the following: (1) distinguishing neuropathological features; (2) alterations in perivascular protein expression; and (3) genotype-specific associations. More widespread Abeta-plaque pathology was observed in AD cases with capillary CAA than in those without. Expression of perivascular excitatory amino acid transporter 2 (EAAT-2/GLT-1) was reduced in cortical astrocytes of AD cases with capillary CAA in contrast to those lacking capillary Abeta-deposition and controls. Genetically, AD cases with capillary CAA were strongly associated with the APOE epsilon4 allele compared to those lacking capillary CAA and to controls. To further validate the existence of distinct types of AD we analyzed polymorp…
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“Capillary CAA is also linked to APOE4 and a variant (C766T (rs1799986)) in the LDL receptor related protein 1 (LRP-1), a receptor for apolipoproteins, which suggests that capillary CAA my also represent a subtype of AD [105, 106].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [105]
In the citing paper
“Many studies demonstrated that ApoE coaggregates with both parenchymal plaques and CAA [30,31].”
From Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease (2017) · cites this paper as [31]
In the citing paper
“They likely are a resultant of multiple genetic features extending beyond APOE genotype as no APOE allelic variant confers absolute protection against VAβ deposition [42, 43].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [43]
In the citing paper
“They likely are a resultant of multiple genetic features extending beyond APOE genotype as no APOE allelic variant confers absolute protection against VAβ deposition [42, 43].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [43]
In the citing paper
“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 [43]
In the citing paper
“Of note, although CAA typically affects leptomeningeal and cortical medium- and small-sized arteries, a subtype of capillary CAA has been associated with APOEε4 carriage51,52.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [52]
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Cited by
Sorted by citations
The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329
“Capillary CAA is also linked to APOE4 and a variant (C766T (rs1799986)) in the LDL receptor related protein 1 (LRP-1), a receptor for apolipoproteins, which suggests that capillary CAA my also represent a subtype of AD [105, 106].”
BackgroundCerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947
Charidimou, A., Gang, Q., & Werring, D. J. (2012) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2011-301308 · Cited by 611
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised
Frisoni, G. B., Altomare, D., Thal, D. R., Ribaldi, F., van der Kant, R., Ossenkoppele, R., Blennow, K., Cummings, J., van Duijn, C., Nilsson, P. M., et al. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00533-w · Cited by 513
Self-citationNeuropathology of Alzheimer's Disease
Trejo‐Lopez, J. A., Yachnis, A. T., & Prokop, S. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01146-y · Cited by 419
Metadata
- Authors
- Thal, D. R., Papassotiropoulos, A., Saido, T. C., Griffin, W. S. T., Mrak, R. E., Kölsch, H., Tredici, K. D., Attems, J., & Ghebremedhin, E.
- Affiliations
- Universität Ulm (DE)
- University of Basel (CH)
- RIKEN Center for Brain Science (JP)
- University of Arkansas Medical Center (US)
- University of Toledo (US)
- University of Bonn (DE)
- Newcastle University (GB)
- Goethe University Frankfurt (DE)
- Corresponding author
- Thal, Dietmar Rudolf
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2010-06-10
- Volume
- 120
- Issue
- 2
- Pages
- 169-183
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2019718390
- Cited by
- 103
- References
- 90
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 7 · 2023: 2 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 6 · 2015: 10 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 12411, P01AG012411)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- sporadic Alzheimer's disease, APOE ε4, amyloid-beta deposition, Alzheimer's disease subtypes, astrocytes, alpha2-macroglobulin receptor, amyloid plaques
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Capillaries, Female, Genotype, Glial Fibrillary Acidic Protein, Humans, Lipoproteins, LDL, Male, Middle Aged, Models, Biological, Psychiatric Status Rating Scales, Odds Ratio, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Excitatory Amino Acid Transporter 2
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