Tau protein (paired helical filament)

Tau protein is a neuronal microtubule-associated protein that plays a crucial role in stabilizing microtubules in neurons. In Alzheimer's disease and other tauopathies, tau undergoes abnormal aggregation to form insoluble fibers known as paired helical filaments (PHFs). These PHFs are the primary component of neurofibrillary tangles, one of the defining pathological features of Alzheimer’s disease. In healthy neurons, tau stabilizes axonal microtubules. In disease states like Alzheimer’s, hyperphosphorylation or other modifications reduce its affinity for microtubules, promoting self-association into PHFs. Accumulation of PHFs disrupts cellular function leading to neurodegeneration.