Genetics of dementia.
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.
School of Public Health, University of Sydney, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia; Huntington Disease Service, Westmead Hospital, Westmead, NSW, Australia.
Clement T
CT
Loy
Neuroscience Research Australia, Randwick, NSW, Australia; University of New South Wales, Kensington, NSW, Australia.
Peter R
PR
Schofield
Department of Medical Genetics, Sydney Children's Hospital, Randwick, NSW, Australia.
Anne M
AM
Turner
Neuroscience Research Australia, Randwick, NSW, Australia; University of New South Wales, Kensington, NSW, Australia. Electronic address: j.kwok@neura.edu.au.
John B J
JB
Kwok
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics; D003704:Dementia / Q000175:diagnosis / Q000235:genetics*; D005817:Genetic Counseling / Q000379:methods; D008040:Genetic Linkage / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype