The range of tau pathology identified in FTDP-17 recapitulates that in sporadic tauopathies, indicating a major role for tau dysfunction in these diseases.
Imbalance of neuronal proteostasis associated with misfolding and aggregation of Tau protein is a common neurodegenerative feature in Alzheimer's disease (AD) and other Tauopathies.
The tauopathies are a group of disorders characterised by aggregation of the microtubule-associated protein tau and include Alzheimer's disease (AD) and the fronto-temporal dementias (FTD).
Progressive accumulation of highly phosphorylated tau protein isoforms is the main feature of a group of neurodegenerative diseases collectively called tauopathies.
Mitochondrial dysfunction and oxidative stress play an important role in ageing and have been implicated in several age-related neurodegenerative conditions including Alzheimer's disease (AD) and other tauopathies characterized by the presence of intracellular accumulations of the hyperphosphorylated microtubule-associated protein tau.
Animal models of neurodegeneration induced by neuronal expression of truncated tau protein emerge as an important tool for understanding the pathogenesis of human tauopathies and for therapy development.
Despite the advent of novel therapeutic approaches and the increasing number of clinical trials in tauopathies, accurate clinical diagnosis is still an unmet need and better tau biomarkers are still desperately needed.
Tauopathies are subclassified according to the predominant species of tau that accumulates, with respect to alternative splicing of MAPT, with tau proteins containing three (3R) or four repeats (4R) of ~32 amino acids in the microtubule binding domain.
The tauopathies are characterized by abnormal deposition of microtubule associated protein tau into intracellular neurofibrillary tangles composed mainly of the hyperphosphorylated form of the protein.
Thus, alterations in the amount of the tau protein, missense mutations, posttranscriptional modifications like phosphorylation, aberrant tau aggregation or a different expression of some of its isoforms could provoke pathological effects resulting in the appearance of neuronal disorders known as tauopathies.
Aggregation of the microtubule-associated protein, tau, can lead to neurofibrillary tangle formation in neurons and glia which is the hallmark of tauopathy.
The formation of intraneuronal fibrillar inclusions of tau protein is associated with several neurodegenerative diseases referred to as tauopathies including Alzheimer's disease (AD).
Microtubule-associated protein tau is the major component of the filamentous neurofibrillary lesions of Alzheimer's disease (AD) and other tauopathies.
Since in Alzheimer's disease and related tauopathies tau proteostasis is compromised, here we sought to understand the role of tau protein in neuronal circadian biology and related behavior.
The microtubule-associated protein tau, in a hyperphosphorylated form, aggregates into insoluble paired-helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies.
This study demonstrates that cells actively release Tau in the absence of disease or toxicity, and Tau release is modified by changes in the Tau protein that are associated with tauopathies.
Tau pathology is also observed in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and other related diseases, so called tauopathies.
We have extensively analyzed the biochemical and histochemical profiles of the tau protein from the rTg4510 transgenic mouse model in which the animals uniquely develop forebrain tau pathologies similar to those found in human tauopathies.
Pathological tau protein inclusions have long been recognized to define the diverse range of neurodegenerative disorders called the tauopathies, which include Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration.
A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions.