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Capillary cerebral amyloid angiopathy in Alzheimer’s disease: association with allocortical/hippocampal microinfarcts and cognitive decline

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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.

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Acknowledgements

This study was funded by grants from Alzheimer Forschung Initiative (AFI) Grant no.: #13803 (DRT); Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO- G0F8516 N Odysseus) (DRT), Vlaamse Impulsfinanciering voor Netwerken voor Dementie-onderzoek (IWT 135043) (DRT), the German Federal Ministry of Education and Research (FTLDc O1GI1007A) (MO), the EU (FAIRPARKII 633190) (MO), the foundation of the state Baden-Württemberg (D.3830) (MO), Thierry Latran Foundation (MO), ALS Association (MO), and BIU(MO). The authors gratefully thank Ms. Alicja Ronisz, Marta Koper, Irina Kosterin, Christine Schneider, Kathrin Pruy, Daniela Demharter, and Alice Yeates for technical help. We acknowledge the help of Ms. Jill Holbrook and Sandra Tomé for reading the manuscript.

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Authors and Affiliations

  1. Laboratory of Neuropathology, Institute of Pathology, University of Ulm, Ulm, Germany

    Moritz Hecht, Lara Maria Krämer & Dietmar Rudolf Thal

  2. Department of Neurology, University of Ulm, Ulm, Germany

    Christine A. F. von Arnim & Markus Otto

  3. Clinic for Neurogeriatrics and neurological Rehabilitation, University- und Rehabilitation Hospital Ulm (RKU), Ulm, Germany

    Christine A. F. von Arnim

  4. Departement Neurowetenschappen, Katholieke Universiteit Leuven, Herestraat 49, Leuven, Belgium

    Dietmar Rudolf Thal

  5. Departement Pathologische Ontleedkunde, UZ Leuven, Leuven, Belgium

    Dietmar Rudolf Thal

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  1. Moritz Hecht
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Correspondence to Dietmar Rudolf Thal.

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Conflict of interest

DRT received consultant honorary from GE-Healthcare and Covance Laboratories and collaborated with Novartis Pharma AG, and Janssen Pharmaceutical Companies. CAFVA received research support from Roche Diagnostics, Biologische Heilmittel Heel, and ViaMed, honoraria from serving on the scientific advisory board of Nutricia, and received speaker honoraria from Nutricia, Lilly Germany, Desitin Arzneimittel, Biogen and Dr. Willmar Schwabe GmbH&Co.KG.

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Hecht, M., Krämer, L.M., von Arnim, C.A.F. et al. Capillary cerebral amyloid angiopathy in Alzheimer’s disease: association with allocortical/hippocampal microinfarcts and cognitive decline. Acta Neuropathol 135, 681–694 (2018). https://doi.org/10.1007/s00401-018-1834-y

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  • DOI: https://doi.org/10.1007/s00401-018-1834-y

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