New developments in frontotemporal dementia and parkinsonism linked to chromosome 17.
OBJECTIVE
The identification of tau mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has revealed invaluable information regarding the role of the tau protein in neurodegenerative disease. Over the past year several new mutations have been identified, and experimental studies have provided further insight into the mechanism of neurodegeneration due to tau mutations and possible interactions with amyloid pathology.


RESULTS
Extensive clinical and pathological variation is seen in patients with different types of mutation, as well as in patients with the same mutation. Mutations may be found in patients with frontotemporal dementia (FTD), parkinsonism, progressive supranuclear palsy and corticobasal degeneration, justifying mutation analysis in familial cases of these disorders. Genetic heterogeneity exists in frontotemporal dementia, because a number of FTDP-17 families have neither tau mutations nor tau pathology. Genetic linkage has been found in familial FTD (chromosome 3), FTD with amyotrophic lateral sclerosis (9q21-q22), and FTD with inclusion body myopathy (9q13.3-p12). Tau deposits may consist of mainly mutated protein, or of mutated and wild-type protein in equal amounts, depending on the mutation. Recent animal studies show that amyloid-beta deposition may accelerate formation of neurofibrillary tangles.


CONCLUSIONS
Hopefully, the identification of responsible genetic defects and associated proteins will be helpful in improving our understanding of the role of the tau protein in the common neurodegenerative process of frontotemporal degeneration.
Rosso
Sonia M
SM
Department of Neurology, Erasmus Medical Centre, University Hospital-Dijkzigt, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
van Swieten
John C
JC
D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000235:genetics*; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype