a1 Institute of Neuropathology, University Hospital of Zürich, Switzerland.
a2 Institute of Pathology, Department of Neuropathology, University of Basel, Switzerland.
a3 Department of Pathology, University of British Columbia, Vancouver, Canada.
Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. Familial FTD has been linked to mutations in several genes, including those encoding the microtubule-associated protein tau (MAPT), progranulin (GRN), valosin-containing protein (VCP) and charged multivescicular body protein 2B (CHMP2B). The associated neuropathology is characterised by selective degeneration of the frontal and temporal lobes (frontotemporal lobar degeneration, FTLD), usually with the presence of abnormal intracellular protein accumulations. The current classification of FTLD neuropathology is based on the identity of the predominant protein abnormality, in the belief that this most closely reflects the underlying pathogenic process. Major subgroups include those characterised by the pathological tau, TDP-43, intermediate filaments and a group with cellular inclusions composed of an unidentified ubiquitinated protein. This review will focus on the current understanding of the molecular basis of each of the major FTLD subtypes. It is anticipated that this knowledge will provide the basis of future advances in the diagnosis and treatment of FTD.
c1 Corresponding author: Ian R.A. Mackenzie, Department of Pathology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, British Columbia, V5Z 1M9, Canada. Tel: +1 604 875 4480; Fax: +1 604 875 5707; E-mail: email@example.com