Current Understanding of Neurodegenerative Diseases Associated With the Protein Tau

Primary tauopathies are a group of neurodegenerative diseases in which tau is believed to be the major contributing factor of the neurodegenerative process. In primary tauopathies, there is a disassociation between tau (a microtubule-associated protein) and microtubules as a result of tau hyperphosphorylation. This disassociation between tau and microtubules results in tau fibrillization and inclusion formation as well as in microtubule dysfunction. There are different clinical syndromes associated with different primary tauopathies, and some clinical syndromes can be associated with multiple primary tauopathies. Hence, although some clinical syndromes are highly specific and almost diagnostic of a primary tauopathy, many are not, making it difficult to diagnose a primary tauopathy. Recently, radioligands that bind to tau and can be combined with positron emission tomography to detect fibrillary tau antemortem have been developed, although preliminary data suggest that these ligands may not be sensitive in detecting tau associated with many primary tauopathies. Another recent advancement in the field is evidence suggesting that tau may exhibit properties similar to those of prions, although infective transmission has not been shown. There have been a few clinical trials targeting tau and microtubule dysfunction, although none have had any disease-modifying effects. Understanding tau biology is critical to the development of pharmacological agents that could have disease-modifying effects on primary tauopathies.