Cited by 105Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchIntracerebral and Subarachnoid Hemorrhage Research

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Capillary cerebral amyloid angiopathy identifies a distinct APOE ε4-associated subtype of sporadic Alzheimer’s disease

Thal, Dietmar Rudolf, Papassotiropoulos, Andreas, Saido, Takaomi C., Griffin, W. Sue T., Mrak, Robert E., Kölsch, Heike, Tredici, Kelly Del, Attems, Johannes, Ghebremedhin, Estifanos·2010·Acta Neuropathologica

DOI 10.1007/s00401-010-0707-9

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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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Additional file 3 of Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier – phenotypic variability in autosomal dominant Alzheimer’s disease
Lloyd, G. M., Trejo‐Lopez, J. A., Xia, Y., McFarland, K. N., Lincoln, S., Ertekin-Taner, N., Giasson, B. I., Yachnis, A. T., & Prokop, S. (2020) · Figshare · doi:10.6084/m9.figshare.11978586
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Self-citation
Additional file 1 of Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier – phenotypic variability in autosomal dominant Alzheimer’s disease
Lloyd, G. M., Trejo‐Lopez, J. A., Xia, Y., McFarland, K. N., Lincoln, S., Ertekin-Taner, N., Giasson, B. I., Yachnis, A. T., & Prokop, S. (2020) · Figshare · doi:10.6084/m9.figshare.11978577

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: Thal, Dietmar Rudolf
Papassotiropoulos, Andreas
Saido, Takaomi C.
Griffin, W. Sue T.
Mrak, Robert E.
Tredici, Kelly Del
Attems, Johannes
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2010-06-10
Volume: 120
Issue: 2
Pages: 169-183
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-010-0707-9
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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Capillary cerebral amyloid angiopathy identifies a distinct APOE ε4-associated subtype of sporadic Alzheimer’s disease

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