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Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline.
Acta Neuropathol. 2018 05; 135(5):681-694.AN

Abstract

Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related Aβ plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.

Authors+Show Affiliations

Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Ulm, Germany.Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Ulm, Germany.Department of Neurology, University of Ulm, Ulm, Germany. Clinic for Neurogeriatrics and neurological Rehabilitation, University- und Rehabilitation Hospital Ulm (RKU), Ulm, Germany.Department of Neurology, University of Ulm, Ulm, Germany.Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Ulm, Germany. Dietmar.Thal@kuleuven.be. Departement Neurowetenschappen, Katholieke Universiteit Leuven, Herestraat 49, Leuven, Belgium. Dietmar.Thal@kuleuven.be. Departement Pathologische Ontleedkunde, UZ Leuven, Leuven, Belgium. Dietmar.Thal@kuleuven.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29574591

Citation

Hecht, Moritz, et al. "Capillary Cerebral Amyloid Angiopathy in Alzheimer's Disease: Association With Allocortical/hippocampal Microinfarcts and Cognitive Decline." Acta Neuropathologica, vol. 135, no. 5, 2018, pp. 681-694.
Hecht M, Krämer LM, von Arnim CAF, et al. Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline. Acta Neuropathol. 2018;135(5):681-694.
Hecht, M., Krämer, L. M., von Arnim, C. A. F., Otto, M., & Thal, D. R. (2018). Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline. Acta Neuropathologica, 135(5), 681-694. https://doi.org/10.1007/s00401-018-1834-y
Hecht M, et al. Capillary Cerebral Amyloid Angiopathy in Alzheimer's Disease: Association With Allocortical/hippocampal Microinfarcts and Cognitive Decline. Acta Neuropathol. 2018;135(5):681-694. PubMed PMID: 29574591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline. AU - Hecht,Moritz, AU - Krämer,Lara Maria, AU - von Arnim,Christine A F, AU - Otto,Markus, AU - Thal,Dietmar Rudolf, Y1 - 2018/03/24/ PY - 2018/01/14/received PY - 2018/03/08/accepted PY - 2018/03/08/revised PY - 2018/3/27/pubmed PY - 2019/7/2/medline PY - 2018/3/26/entrez KW - Alzheimer KW - Cerebral amyloid angiopathy KW - Cognitive decline KW - Dementia KW - Hippocampus KW - Microinfarct SP - 681 EP - 694 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 135 IS - 5 N2 - Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related Aβ plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/29574591/Capillary_cerebral_amyloid_angiopathy_in_Alzheimer's_disease:_association_with_allocortical/hippocampal_microinfarcts_and_cognitive_decline_ L2 - https://dx.doi.org/10.1007/s00401-018-1834-y DB - PRIME DP - Unbound Medicine ER -