Neurodegenerative diseases as diverse as Alzheimer’s disease (AD) and Parkinson's disease (PD) share the common feature of aggregation and accumulation of abnormal proteins. A large group of these diseases, known as the tauopathies, are characterized by filamentous lesions in neurons that are composed of aggregates of hyperphosphorylated tau, known as neurofibrillary tangles (NFTs).
Tau promotes microtubule (MT) assembly, reduces MT instability and plays a role in maintaining neuronal integrity and axonal transport. During the development of NFTs, tau becomes hyperphosphorylated, detaches from the axonal microtubules and aggregates. The abnormal tau eventually accumulates in filamentous inclusions within neuronal cell bodies. The precise sequence of events and the mechanisms involved in this process are not fully understood, but it is clear that abnormal NFT accumulation and aggregation are sufficient to cause neurodegeneration. This in turn leads progressively to the onset of clinical symptoms.