Tauopathy

Last revised by Dr Ali Alsmair on 23 Dec 2021

Tauopathies are a heterogeneous group of neurodegenerative diseases characterised 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 neurones and glial cells. 

Examples of tauopathies include 3:

Terminology

It should be noted that some texts 2 define tauopathies as a disease characterised 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 5

Pathophysiology

Tauopathies are the result of aggregation and precipitation of misfolded τ proteins that normally stabilise 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 5

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 4.

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Cases and figures

  • Progressive supranuclear palsy
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