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Current Neurology and Neuroscience Reports
Published in: Current Neurology and Neuroscience Reports 11/2014

Open Access 01-11-2014 | Dementia (KS Marder, Section Editor)

Genetic Heterogeneity in Alzheimer Disease and Implications for Treatment Strategies

Authors: John M. Ringman, Alison Goate, Colin L. Masters, Nigel J. Cairns, Adrian Danek, Neill Graff-Radford, Bernardino Ghetti, John C. Morris, Dominantly Inherited Alzheimer Network

Published in: Current Neurology and Neuroscience Reports | Issue 11/2014

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Abstract

Since the original publication describing the illness in 1907, the genetic understanding of Alzheimer’s disease (AD) has advanced such that it is now clear that it is a genetically heterogeneous condition, the subtypes of which may not uniformly respond to a given intervention. It is therefore critical to characterize the clinical and preclinical stages of AD subtypes, including the rare autosomal dominant forms caused by known mutations in the PSEN1, APP, and PSEN2 genes that are being studied in the Dominantly Inherited Alzheimer Network study and its associated secondary prevention trial. Similar efforts are occurring in an extended Colombian family with a PSEN1 mutation, in APOE ε4 homozygotes, and in Down syndrome. Despite commonalities in the mechanisms producing the AD phenotype, there are also differences that reflect specific genetic origins. Treatment modalities should be chosen and trials designed with these differences in mind. Ideally, the varying pathological cascades involved in the different subtypes of AD should be defined so that both areas of overlap and of distinct differences can be taken into account. At the very least, clinical trials should determine the influence of known genetic factors in post hoc analyses.
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Metadata
Title
Genetic Heterogeneity in Alzheimer Disease and Implications for Treatment Strategies
Authors
John M. Ringman
Alison Goate
Colin L. Masters
Nigel J. Cairns
Adrian Danek
Neill Graff-Radford
Bernardino Ghetti
John C. Morris
Dominantly Inherited Alzheimer Network
Publication date
01-11-2014
Publisher
Springer US
Published in
Current Neurology and Neuroscience Reports / Issue 11/2014
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI
https://doi.org/10.1007/s11910-014-0499-8

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