Tauopathy

Tauopathy belongs to a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing the protein to dissociate from microtubules and form aggregates in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as paired helical filaments). The precise mechanism of tangle formation is not completely understood, and it is still controversial as to whether tangles are a primary causative factor in the disease or play a more peripheral role. Ankyrin: Long QT syndrome 4 Tauopathy belongs to a class of neurodegenerative diseases associated with the pathological aggregation of tau protein in neurofibrillary or gliofibrillary tangles in the human brain. Tangles are formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing the protein to dissociate from microtubules and form aggregates in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as paired helical filaments). The precise mechanism of tangle formation is not completely understood, and it is still controversial as to whether tangles are a primary causative factor in the disease or play a more peripheral role. Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients suffering from Alzheimer's disease (AD), which is considered a secondary tauopathy. AD is also classified as an amyloidosis because of the presence of senile plaques. When tau becomes hyperphosphorylated, the protein dissociates from the microtubules in axons. Then, tau becomes misfolded and the protein begins to aggregate, which eventually forms the neurofibrillary tangles seen in Alzheimer’s patients. Microtubules also destabilize when tau is dissociated. The combination of the neurofibrillary tangles and destabilized microtubules result in disruption of processes such as axonal transport and neural communication. The degree of NFT involvement in AD is defined by Braak stages. Braak stages I and II are used when NFT involvement is confined mainly to the transentorhinal region of the brain, stages III and IV when there's also involvement of limbic regions such as the hippocampus, and V and VI when there's extensive neocortical involvement. This should not be confused with the degree of senile plaque involvement, which progresses differently. In both Pick's disease and corticobasal degeneration, tau proteins are deposited as inclusion bodies within swollen or 'ballooned' neurons. Argyrophilic grain disease (AGD), another type of dementia, is marked by an abundance of argyrophilic grains and coiled bodies upon microscopic examination of brain tissue. Some consider it to be a type of Alzheimer's disease. It may co-exist with other tauopathies such as progressive supranuclear palsy and corticobasal degeneration, and also Pick's disease. Tauopathies are often overlapped with synucleinopathies, possibly due to interaction between the synuclein and tau proteins. The non-Alzheimer's tauopathies are sometimes grouped together as 'Pick's complex' due to their association with frontotemporal dementia, or frontotemporal lobar degeneration.