Tauopathies

Tauopathies are a group of neurological disorders characterized by the accumulation of abnormal aggregates of the microtubule associated protein Tau in neurons in the brain. Tau accumulation contributes to the injury and death of neurons, resulting in a range of manifestations from mild cognitive impairment to coma and death. Tauopathies are autosomal dominant neurological disorders. Early signs of tauopathy include subtle changes in behavior, language, and vision, as well as memory deficits and struggles with executive functioning. As the disease progresses into more advanced stages, difficulties walking, balance, and other motor functions can become more prominent. Tau accumulates in neurons as clusters of filamentous aggregates or neurofibrillary tangles. In normal neurons, tau binds to and stabilizes the microtubules. In tauopathies, the levels of tau in the brain are increased, resulting in impaired function of the microtubules and subsequent cell death. Various genetic mutations of tau (targeting the amino acid sequence of tau protein) have been associated with tauopathies, such as frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration. The exact causes of tauopathy are disputed. A variety of environmental, genetic, and physiological factors may all contribute to Tau accumulation. Oxidative stress, infection, age-related inflammation, and reduced activity of degradative pathways (such as autophagy) have all been proposed as potential sources of tauopathy. In addition, genetic sequencing of the Tau gene (MAPT) in individuals with tauopathies has identified a number of mutations that may contribute to tau accumulation. The diagnosis of tauopathies is primarily through clinical evaluation of symptoms and imaging. Biomarkers of tauopathy (e.g. CSF tau) may be used to aid in the diagnosis. Current treatments for tauopathies focus on symptomatic relief, mainly through medications that improve cognitive functions.