In addition to the tau mutations, a common extended haplotype in the tau gene also appears to be a risk factor in the development of the apparently sporadic tauopathies progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
We show that the entire, fully extended H1 haplotype is associated with PSP, which implicates several other genes in addition to MAPT, as candidate pathogenic loci.
Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration.
We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features.
Using 15 haplotype tagging SNPs (htSNPs), capturing >95% of MAPT haplotype diversity, we performed association analysis in a US sample of 274 predominantly pathologically confirmed PSP patients and 424 matched control individuals.
Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 haplotype of MAPT, the gene encoding tau, is the major risk factor in PSP.
Mutations in the tau gene, MAPT, cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and common variation in MAPT is strongly associated with the risk of PSP, corticobasal degeneration and, to a lesser extent, AD and Parkinson's disease (PD), implicating the involvement of tau in common neurodegenerative pathway(s).
Despite recent discoveries of the strong genetic association of sporadic progressive supranuclear palsy with tau gene polymorphisms, a specific risk allele for developing the palsy has not yet been identified yet.
Tauopathies, including Alzheimer's disease (AD), fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease and progressive supranuclear palsy, are neurodegenerative disorders neuropathologically characterized by the presence of intraneuronal fibrillary inclusions composed of abnormally phosphorylated-Tau.
Tauopathies are a group of neurodegenerative disorders that include hereditary frontotemporal dementias (FTDs) such as FTD with parkinsonism linked to chromosome 17 (FTDP-17), as well as sporadic variants of FTDs like progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick's disease.
In addition, the recent identification of mutations in the tau gene associated with a similar neurodegenerative condition (frontotemporal dementia and parkinsonism linked to chromosome 17) has further strengthened the argument that tau dysfunction is somehow involved in the pathogenesis of PSP.
Accumulation of microtubule associated protein tau in the substantia nigra is associated with several tauopathies including progressive supranuclear palsy (PSP).