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.
Neuropathological examination confirmed the PSP diagnosis in the first two subjects; the MAPTP301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in gray and white matter with heaviest burden in basal ganglia.
Our results suggest that abnormalities in the alternative splicing of the tau gene are involved in the molecular mechanism related to PSP pathogenesis.
Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), sporadic multisystem tauopathy, and some forms of frontotemporal dementia with Parkinsonism linked to chromosome 17 are characterized by neuronal and glial lesions accumulating tau protein containing 4 conserved repeats in microtubule-binding domain (4R tau).
These data argue that additional genes may confer disease risk to PSP and CBS, and to FTD as well, beyond the MAPT tau haplotype.Further studies are warranted.
Gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in AD, sPD, sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2, Pick's disease (PiD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration linked to mutation P301L in MAPT Frontotemporal lobar degeneration-tau (FTLD-tau).
However, in the sporadic tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) where MAPT mutation is absent, common variation in MAPT that defines the H1 and H2 haplotype clades strongly influences disease risk.
The aim of the present study is to investigate UPR activation in sporadic tauopathies like progressive supranuclear palsy (PSP) and Pick's disease (PiD), and familial cases with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) which carry mutations in the gene encoding for tau (MAPT).
The MAPT H1 haplotype has been associated with four-repeat (4R) tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease.
We have recently examined the MAPT locus in progressive supranuclear palsy and found that a haplotype (H1c) on the background of the well-described H1 clade is associated with PSP.
Two recent studies investigated the association of the microtubule associated protein tau (MAPT) H1 haplotype, a known risk factor for neurodegenerative disease including progressive supranuclear palsy and Parkinson's disease (PD), with essential tremor (ET).