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Neuropathology of Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type

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Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders

Abstract

Hereditary cerebral hemorrhage with amyloidosis-Dutch type is caused by an amyloid β (Aβ) precursor protein (APP) gene codon 693 mutation, producing a Gln-for-Glu substitution at residue 22 of Aβ. In vitro, the mutation alters the proteolytic processing of APP, increasing the relative quantities of full-length Aβ beginning at Asp1, and of truncated Aβ peptides beginning at Val18 and Phe19, and Aβ peptides with the amino acid substitution exhibit an increased tendency for fibril formation; in vivo, the mutation accelerates primarily the deposition of amyloid in cerebral blood vessel walls, resulting in severe amyloid angiopathy with secondary microvascular degeneration and hence cerebral hemorrhages and/or infarcts. Brain parenchymal Aβ deposition is also enhanced but plaque formation is not essentially associated with neurofibrillary degeneration. Evidence suggests similarities between early events in the development of cerebral amyloid angiopathy and senile plaques.

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Authors and Affiliations

  1. Departments of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands

    Marion L. C. Maat-Schieman, Remco Natté & Raymund A. C. Roos

  2. Departments of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands

    Sjoerd G. Van Duinen

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  1. Marion L. C. Maat-Schieman
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  2. Sjoerd G. Van Duinen
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Editors and Affiliations

  1. Departments of Neurology and Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

    Marcel M. Verbeek

  2. Department of Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

    Robert M. W. de Waal

  3. UCLA Medical Center, Los Angeles, CA, USA

    Harry V. Vinters

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Maat-Schieman, M.L.C., Van Duinen, S.G., Natté, R., Roos, R.A.C. (2000). Neuropathology of Hereditary Cerebral Hemorrhage with Amyloidosis-Dutch Type. In: Verbeek, M.M., de Waal, R.M.W., Vinters, H.V. (eds) Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1007-7_13

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