Christine Johanna Band Schmidt

[18F]-Florbetapir PET distinguishes Frontotemporal Dementia from Alzheimer's Disease.

Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. The genetics of FTD has been one of the success stories in genetics over the past 15 years. Classic family based linkage studies have identified genes that explain a large part of the families with a Mendelian inheritance of the disease. This group of familial FTD patients has now been linked to mutations in several genes, including the microtubule-associated protein tau (MAPT), progranulin (GRN), valosin-containing protein (VCP), charged multivescicular body protein 2B (CHMP2B), TAR DNA-binding protein 43 (TDP43) and Fused in Sarcoma (FUS) and most recently C9Orf72. Over the years the identified genes have triggered many studies that increased our understanding of the disease process. Neuropathologically the disease can be divided in two major groups that have a clear correlation with their genetic background; hose with tau-positive inclusions and those with ubiquitin-positive and TDP43 positive inclusions. The field of genetics keeps changing rapidly thanks to technological developments, first with the development of Genome Wide Association Studies (GWAS) studies but now also with the use of next generation sequencing, as was already demonstrated with the identification of the expanded repeat in C9Orf72, and we can also expect many whole exome or whole genome sequencing studies. This review provides an overview of the genetics of FTD, with an update of recent discoveries.