Title |
Discovery and validation of autosomal dominant Alzheimer’s disease mutations
|
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Published in |
Alzheimer's Research & Therapy, July 2018
|
DOI | 10.1186/s13195-018-0392-9 |
Pubmed ID | |
Authors |
Simon Hsu, Brian A. Gordon, Russ Hornbeck, Joanne B. Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S. Day, Eric McDade, John C. Morris, Anne M. Fagan, Tammie L. S. Benzinger, Alison M. Goate, Carlos Cruchaga, Randall J. Bateman, Dominantly Inherited Alzheimer Network (DIAN), Celeste M. Karch |
Abstract |
Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes. In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses. We propose that PSEN1 M84V, PSEN1 A396T, PSEN2 R284G, and APP T719N are likely pathogenic mutations, whereas PSEN1 c.379_382delXXXXinsG and PSEN2 L238F have uncertain pathogenicity. In defining a subset of these variants as pathogenic, individuals from these families can now be enrolled in observational and clinical trials. This study outlines a critical approach for translating genetic data into meaningful clinical outcomes. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 4 | 67% |
United Kingdom | 2 | 33% |
Demographic breakdown
Type | Count | As % |
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Scientists | 4 | 67% |
Members of the public | 2 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 77 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 17 | 22% |
Student > Ph. D. Student | 12 | 16% |
Student > Bachelor | 8 | 10% |
Student > Master | 4 | 5% |
Other | 3 | 4% |
Other | 10 | 13% |
Unknown | 23 | 30% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 12 | 16% |
Neuroscience | 12 | 16% |
Medicine and Dentistry | 11 | 14% |
Agricultural and Biological Sciences | 4 | 5% |
Psychology | 3 | 4% |
Other | 9 | 12% |
Unknown | 26 | 34% |