Frontotemporal dementia: from Mendelian genetics towards genome wide association studies

Frontotemporal lobar degeneration is the most common cause of dementia of non-Alzheimer's type worldwide. It manifests, clinically, with behavioural changes and language impairment and is pathologically associated with tau- or ubiquitin-positive inclusions detected in neurons and glial cells of the frontal and temporal lobes in the brain. Genetic variations in the microtubule-associated protein tau and progranulin genes explain almost 50% of familial cases, whilst variations in TAR DNA-binding protein, charged multivescicular body protein 2B, valosin-containing protein and fused in sarcoma genes contribute to <5% of cases. The rapidly developing investigative techniques available to geneticists such as genome-wide association studies, whole-exome sequencing and, soon, whole-genome sequencing promise to contribute to the unravelling of the genetic architecture of this complex disease and, in the future, to the development of more sensitive, accurate and effective diagnostic and treatment measures.