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Genetic Complexity of Early-Onset Alzheimer’s Disease

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Neurodegenerative Diseases

Abstract

The recent advances in “omics” technologies (e.g., next-generation sequencing) have made the precision medicine possible. Knowledge about genetics of Alzheimer’s disease (AD), the most prevalent form of dementia, is important to manage the challenges of aging populations. So far, genetic analyses of families with autosomal dominant AD, presenting with early-onset dementia (<65 years of age), have found three causal genes: APP, PSEN1, and PSEN2. Genetics is now widely applied to AD diagnosis, monitoring, and the search for a potential treatment. The ability to detect carriers of causal mutations could help to evaluate the efficacy of AD therapies in the longitudinal clinical trials of the individuals at either pre-symptomatic or early stages of dementia. We provide an overview for the molecular genetic findings available for early-onset AD; discuss how this knowledge can be applied in clinical practice and highlight strategies to detect novel AD genes.

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Acknowledgements

We are grateful for the support from the Canadian Institutes of Health Research, Wellcome Trust, Medical Research Council, National Institutes of Health, and the Canadian Consortium on Neurodegeneration in Aging.

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Authors and Affiliations

  1. Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada

    Mahdi Ghani, Peter St George-Hyslop & Ekaterina Rogaeva

  2. Departments of Neurology, and Epidemiology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA

    Christiane Reitz

  3. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Peter St George-Hyslop & Ekaterina Rogaeva

  4. Department of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK

    Peter St George-Hyslop

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  1. Mahdi Ghani
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  2. Christiane Reitz
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  3. Peter St George-Hyslop
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  4. Ekaterina Rogaeva
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Correspondence to Ekaterina Rogaeva .

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  1. University of Milan, Fondazione Ca’ Granda, IRCCS Ospedale Policlinico, Milan, Italy

    Daniela Galimberti

  2. University of Milan, Fondazione Ca’ Granda, IRCCS Ospedale Policlinico, Milan, Italy

    Elio Scarpini

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Ghani, M., Reitz, C., George-Hyslop, P.S., Rogaeva, E. (2018). Genetic Complexity of Early-Onset Alzheimer’s Disease. In: Galimberti, D., Scarpini, E. (eds) Neurodegenerative Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-72938-1_3

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