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The Genetics of Dementia
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TLDR
The evidence for, and the approach to, genetic testing in Alzheimer's disease (APP, PSEN1, and PSEN2 genes), frontotemporal dementia (MAPT, GRN, C9ORF72, and other genes), and other familial dementias as mentioned in this paper.Abstract:
25% of all people aged 55 years and older have a family history of dementia. For most, the family history is due to genetically complex disease, where many genetic variations of small effect interact to increase risk of dementia. The lifetime risk of dementia for these families is about 20%, compared with 10% in the general population. A small proportion of families have an autosomal dominant family history of early-onset dementia, which is often due to mendelian disease, caused by a mutation in one of the dementia genes. Each family member has a 50% chance of inheriting the mutation, which confers a lifetime dementia risk of over 95%. In this Review, we focus on the evidence for, and the approach to, genetic testing in Alzheimer's disease (APP, PSEN1, and PSEN2 genes), frontotemporal dementia (MAPT, GRN, C9ORF72, and other genes), and other familial dementias. We conclude by discussing the practical aspects of genetic counselling.read more
Citations
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2016 Alzheimer's disease facts and figures
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Frontotemporal Dementia An Updated Clinician’s Guide
TL;DR: Today, frontotemporal dementia (FTD) remains one of the most common forms of early-onset dementia, that is, before the age of 65, thus posing several diagnostic challenges to clinicians.
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Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis
Scott C. Neu,Judy Pa,Walter A. Kukull,Duane Beekly,Amanda B. Kuzma,Prabhakaran Gangadharan,Li-San Wang,Klaus Romero,Stephen P. Arneric,Alberto Redolfi,Daniele Orlandi,Giovanni B. Frisoni,Rhoda Au,Sherral Devine,Sanford Auerbach,Ana Espinosa,Mercè Boada,Agustín Ruiz,Sterling C. Johnson,Rebecca L. Koscik,Jiun-Jie Wang,Jiun-Jie Wang,Wen Chuin Hsu,Yao Liang Chen,Arthur W. Toga +24 more
TL;DR: Contrary to long-standing views, men and women with the APOE &egr;3/&egR;4 genotype have nearly the same odds of developing AD from age 55 to 85 years, but women have an increased risk at younger ages.
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Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects.
Robert Vassar,Peer-Hendrik Kuhn,Peer-Hendrik Kuhn,Christian Haass,Christian Haass,Matthew E. Kennedy,Matthew E. Kennedy,Lawrence Rajendran,Philip C. Wong,Stefan F. Lichtenthaler +9 more
TL;DR: This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism‐based liabilities, in particular for BACE inhibitors in Alzheimer's disease.
References
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