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

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 +1 more·2010·Acta Neuropathologica

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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Crossref · 10.1007/s00401-010-0707-9

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  • Capillary CAA is linked to APOE4 and a variant (C766T (rs1799986)) in LRP-1, suggesting capillary CAA may represent a subtype of AD.

    “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]

  • ApoE coaggregates with both parenchymal plaques and CAA.

    “Many studies demonstrated that ApoE coaggregates with both parenchymal plaques and CAA [30,31].”
  • No APOE allelic variant confers absolute protection against VAβ deposition.

    “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].”
  • Mechanisms underlying VAβ deposition including preferential development of CAA and CCA likely are a resultant of multiple genetic features extending beyond APOE genotype.

    “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].”
  • 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].”

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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
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
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG 12411, P01AG012411)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › 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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