Tauopathy

This patient
presented with progressive dementia, ataxia and incontinence. A clinical diagnosis of normal pressure hydrocephalus was entertained. Imaging did not support this, however, and on formal testing abnormal nystagmus and eye movements were detected. A sagittal T1-weighted image shows atrophy of the midbrain, with preservation of the volume of the pons. This appearance has been called the "penguin sign". There is also atrophy of the tectum, particularly the superior colliculi. These findings suggest the diagnosis of en:progressive supranuclear palsy.
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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:
Assoziationen und Differentialdiagnosen zu Tauopathie: