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Alzheimer’s Disease and Frontotemporal Dementia: The Current State of Genetics and Genetic Testing Since the Advent of Next-Generation Sequencing

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Abstract

The advent of next-generation sequencing has changed genetic diagnostics, allowing clinicians to test concurrently for phenotypically overlapping conditions such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). However, to interpret genetic results, clinicians require an understanding of the benefits and limitations of different genetic technologies, such as the inability to detect large repeat expansions in such diseases as C9orf72-associated FTD and amyotrophic lateral sclerosis. Other types of mutations such as large deletions or duplications and triple repeat expansions may also go undetected. Additionally, the concurrent testing of multiple genes or the whole exome increases the likelihood of discovering variants of unknown significance. Our goal here is to review the current knowledge about the genetics of AD and FTD and suggest up-to-date guidelines for genetic testing for these dementias. Despite the improvements in diagnosis due to biomarkers testing, AD and FTD can have overlapping symptoms. When used appropriately, genetic testing can elucidate the diagnosis and specific etiology of the disease, as well as provide information for the family and determine eligibility for clinical trials. Prior to ordering genetic testing, clinicians must determine the appropriate genes to test, the types of mutations that occur in these genes, and the best type of genetic test to use. Without this analysis, interpretation of genetic results will be difficult. Patients should be counseled about the benefits and limitations of different types of genetic tests so they can make an informed decision about testing.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 7.103 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA

    Vivianna M. Van Deerlin

  2. Taub Institute, Columbia University Medical Center, 630 W. 168th St., Box 16, New York, NY, 10032, USA

    Jill S. Goldman

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Correspondence to Vivianna M. Van Deerlin.

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VMV and JSG declare no conflicts of interest directly relevant to this study.

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This study was funded by the National Institutes of Health (NIH) (P01-AG-017586, P30 AG-01024, P50 AG-008702) and the New York State Department of Health (C031425).

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Goldman, J.S., Van Deerlin, V.M. Alzheimer’s Disease and Frontotemporal Dementia: The Current State of Genetics and Genetic Testing Since the Advent of Next-Generation Sequencing. Mol Diagn Ther 22, 505–513 (2018). https://doi.org/10.1007/s40291-018-0347-7

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