FTDP-17
Definition: Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant neurodegenerative disorder characterized by behavioural and personality changes, cognitive impairment and motor defects that are caused by mutations in the gene encoding tau. NFTs are abundant in the brain of affected individuals. FTDP-17 is inherited as an autosomal dominant condition, characterized initially by behavioural and motor disturbances that are later associated with cognitive impairment.
Pathology
At autopsy, FTDP-17 patients usually display predominant frontotemporal atrophy with neuronal loss, gliosis and cortical spongiform changes in layer 2.
Neuropathological analysis reveals the presence of abundant intraneuronal tau inclusions, and glial inclusions have also been observed in some families.
Tau is a microtubule-associated protein involved in microtubule assembly and stabilization. Abnormal filamentous tau deposits constitute a major defining characteristic of several neurodegenerative diseases, including Alzheimer?s disease.
Etiology
In 1998, the identification of exonic and intronic tau gene mutations associated with FTDP-17 established that tau dysfunction can cause neurodegeneration.
These findings and subsequent reports have so far identified more than 25 tau mutations, which can be classified according to their positions in the tau gene, their effects on tau mRNA and protein, and the type of tau pathology they lead to.
See also
References
Ingram EM, Spillantini MG. Tau gene mutations: dissecting the pathogenesis of FTDP-17. Trends Mol Med. 2002 Dec;8(12):555-62. PMID: 12470988