Tauopathies

Tauopathies are a heterogeneous group of neurodegenerative diseases characterized by abnormal metabolism of misfolded τ (tau) proteins leading to intracellular accumulation and formation of neurofibrillary tangles (NFT). These neurofibrillary tangles are deposited in the cytosol of neurons and glial cells.

Examples of tauopathies include :

Terminology

It should be noted that some texts define tauopathies as a disease characterized by mutations in the τ protein gene itself. If such a strict definition is used, even though the histopathological hallmark of Alzheimer disease is the presence of numerous neurofibrillary tangles (which are also formed by τ proteins), it still would not be strictly a tauopathy, as no defect in the tau protein gene has been identified. Thus, it is referred to as a secondary tauopathy as β-amyloid accumulation is considered the primary pathology .

Pathophysiology

Tauopathies are the result of aggregation and precipitation of misfolded τ proteins that normally stabilize neural microtubules. These aggregates form neurofibrillary tangles that in turn lead to neuronal toxicity and degeneration.

Misfolded τ proteins from two distinct aggregates: three repeat (3R) and four repeat (4R) which variably present in different diseases .

More recently the discovery of the glymphatic pathway and the importance of this in the normal physiological clearance of extracellular solutes including beta-amyloid, suggests that there is also the possibility of reduced clearance, in addition to abnormal metabolism, as the underpinning of some tauopathies including chronic traumatic encephalopathy .

Siehe auch: