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 Neurofibrillary tangles were first described by Alois Alzheimer in one of his patients suffering from Alzheimer's disease (AD). The tangles are considered a secondary tauopathy. AD is also classified as an amyloidosis because of the presence of senile plaques.[3]   When tau becomes hyperphosphorylated, the protein dissociates from the microtubules in axons.[4] Then, tau becomes misfolded and the protein begins to aggregate, which eventually forms the neurofibrillary tangles seen in Alzheimer’s patients.[1] 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.[5]   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.   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. Tauopathies are characterized by the aberrant modification, splicing, and aggregation of the microtubule-associated protein Tau into filamentous inclusions in neurons and glia. Tau pathology is present across a wide spectrum of neurodegenerative diseases including Alzheimer's disease, fronto-temporal dementias, Pick's disease, progressive supranuclear palsy, chronic traumatic encephalopathy, Huntington's and Parkinson's diseases, among others. Given the combined prevalence of these diseases and the importance of Tau pathology in Alzheimer's disease, research on tauopathy should be considered a priority.    

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