Tauopathies

Tauopathies
Classification and external resources

Tauopathies are a class of neurodegenerative diseases characterized by the pathological aggregation of the tau protein in the human brain. These diseases are marked by the presence of neurofibrillary tangles, which are composed of hyperphosphorylated tau protein. Tauopathies are associated with a range of clinical symptoms, including cognitive decline, motor dysfunction, and behavioral changes.

Pathophysiology

Tau is a microtubule-associated protein that plays a critical role in stabilizing microtubules in neurons. In tauopathies, tau protein becomes abnormally phosphorylated, leading to its detachment from microtubules and subsequent aggregation into insoluble fibrils. This process disrupts neuronal function and ultimately leads to cell death.

The exact mechanisms leading to tau hyperphosphorylation and aggregation are not fully understood, but they are believed to involve a combination of genetic, environmental, and age-related factors. Mutations in the MAPT gene, which encodes the tau protein, have been linked to certain familial forms of tauopathies.

Types of Tauopathies

Tauopathies encompass a variety of disorders, each with distinct clinical and pathological features:

• Alzheimer's disease: Characterized by both amyloid plaques and neurofibrillary tangles.
• Progressive supranuclear palsy (PSP): Marked by vertical gaze palsy and postural instability.
• Corticobasal degeneration (CBD): Features asymmetric motor symptoms and cortical dysfunction.
• Frontotemporal dementia (FTD): Involves changes in personality and behavior, with or without motor symptoms.
• Chronic traumatic encephalopathy (CTE): Associated with repeated head trauma, common in athletes.

Diagnosis

The diagnosis of tauopathies is primarily clinical, supported by neuroimaging and, in some cases, cerebrospinal fluid (CSF) biomarkers. Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans can reveal patterns of brain atrophy and tau deposition, respectively. Genetic testing may be indicated in familial cases.

Treatment

Currently, there is no cure for tauopathies. Treatment focuses on managing symptoms and providing supportive care. Pharmacological interventions may include cholinesterase inhibitors and NMDA receptor antagonists for cognitive symptoms, as well as medications for mood and motor symptoms. Non-pharmacological approaches, such as physical therapy and cognitive rehabilitation, are also important.

Research Directions

Research into tauopathies is ongoing, with efforts focused on understanding the molecular mechanisms of tau aggregation and developing disease-modifying therapies. Potential therapeutic strategies include tau-targeting antibodies, small molecules that inhibit tau aggregation, and gene therapy approaches.

Also see

• Neurodegenerative disease
• Amyloid beta
• Parkinson's disease
• Lewy body dementia