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Alzheimer's Disease, Cerebrovascular Disease, and the β-amyloid Cascade

Published online by Cambridge University Press:  02 December 2014

Kie Honjo ,
Sandra E. Black  and
Nicolaas P. L. G. Verhoeff
Kie Honjo*
Affiliation:
Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada Department of Neurology, Hiroshima University Hospital, Hiroshima, Japan
Sandra E. Black
Affiliation:
Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada
Nicolaas P. L. G. Verhoeff
Affiliation:
Kunin-Lunenfeld Applied Research Unit, Baycrest, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
*
1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima, Japan 734-8551. Email: kiehon@hotmail.com
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Abstract

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Alzheimer's disease (AD), considered the commonest neurodegenerative cause of dementia, is associated with hallmark pathologies including extracellular amyloid-β protein (Aβ) deposition in extracellular senile plaques and vessels, and intraneuronal tau deposition as neurofibrillary tangles. Although AD is usually categorized as neurodegeneration distinct from cerebrovascular disease (CVD), studies have shown strong links between AD and CVD. There is evidence that vascular risk factors and CVD may accelerate Aβ 40-42 production/ aggregation/deposition and contribute to the pathology and symptomatology of AD. Aβ deposited along vessels also causes cerebral amyloid angiopathy. Amyloid imaging allows in vivo detection of AD pathology, opening the way for prevention and early treatment, if disease-modifying therapies in the pipeline show safety and efficacy. In this review, we review the role of vascular factors and Aβ, underlining that vascular risk factor management may be important for AD prevention and treatment.

Résumé

RÉSUMÉ

La maladie d'Alzheimer (MA), considérée comme la cause neurodégénérative de démence la plus fréquente, est associée à des pathologies caractéristiques dont le dépôt extracellulaire de protéine 13-amyloïde (A13) dans les plaques séniles extracellulaires et les vaisseaux et le dépôt intraneuronal de la protéine tau sous forme d'amas neurofibrillaires. Bien que la MA soit habituellement classifiée comme une neurodégénérescence distincte de la maladie cérébrovasculaire (MCV), des études ont montré des liens étroits entre la MA et la MCV. Il existe des données selon lesquelles les facteurs de risque vasculaire et la MCV peuvent accélérer la production/l'agrégation/le dépôt de l'Af3 40-42 et contribuer à la pathologie et à la symptomatologie de la MA. Le dépôt de l'Af3 le long des vaisseaux cause également l'angiopathie amyloïde cérébrale. L'imagerie de l'amyloïde permet la détection in vivo de la pathologie de la MA, ouvrant ainsi la voie à la prévention et au traitement précoces, si des traitements modificateurs de la maladie actuellement en développement s'avèrent sûrs et efficaces. Nous revoyons ici le rôle des facteurs de risque vasculaire et de l'A13, tout en soulignant que le contrôle des facteurs de risque vasculaire peut être important dans la prévention et le traitement de la MA.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 6 , November 2012 , pp. 712 - 728
Copyright
Copyright © The Canadian Journal of Neurological 2012

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