The second part will deal with the recent discovery of tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 which demonstrates that tau dysfunction can lead to neurodegeneration.
Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD).
Autonomic function was investigated in five affected and five at-risk members of a single kinship of pallidopontonigral degeneration (PPND), which is a progressive syndrome of parkinsonism and frontotemporal dementia resulting from a mutation in the N279Ktau gene on chromosome 17.
Pallido-ponto-nigral degeneration (PPND), caused by an N279K mutation of the MAPT gene, is 1 of a family of disorders collectively referred to as frontotemporal dementia and parkinsonism linked to chromosome 17.
Recently, mutations in the tau gene on chromosome 17 were found causative for autosomal dominantly inherited frontotemporal dementia and parkinsonism (FTDP-17).
The identification of mutations in MAPT, the gene that encodes tau, causing dementia and parkinsonism established the notion that tau aggregation is responsible for the development of disease.
The assembly of tau protein into abnormal filaments and brain cell degeneration are characteristic of a number of human neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17.
The role of tau in neurodegeneration has been clarified by the identification of genetic mutations in the tau gene in cases with familial frontotemporal dementia and parkinsonism linked to chromosome 17.
Frontotemporal dementia and parkinsonism linked to chromosome 17 have been associated with mutations in the microtubule associated protein tau (MAPT or tau) gene.
We have previously generated a double transgenic mouse line overexpressing the enzyme GSK-3beta and tau protein carrying a triple frontotemporal dementia and parkinsonism linked to chromosome 17 mutation whose expression patterns overlap in CA1 (pyramidal neurons) and dentate gyrus (granular neurons).
As a result, 2 novel mutations in MAPT (p.D177V and p.P513A) were identified in a sporadic and familial patient with PNFA respectively, and one known mutation in MAPT (p.N279K) was detected in an FTD-parkinsonism family.
Agraphia in patients with frontotemporal dementia and parkinsonism linked to chromosome 17 with P301LMAPT mutation: dysexecutive, aphasic, apraxic or spatial phenomenon?
Carbazole and 2-arylquinoline binding was only observed in cases with Alzheimer's disease and one case with frontotemporal dementia and parkinsonism linked to chromosome 17 exhibiting a R406WMAPT mutation.
The MAPT gene, located on 17q21 and coding for the human microtubule-associated protein tau, is a strong candidate gene, since tau-positive neuronal inclusions have been observed in brains from some FTDP patients.