Neurofibrillary tangles (NFTs) are aggregates of hyperphosphorylated tau protein that are most commonly known as a primary marker of Alzheimer's disease. Their presence is also found in numerous other diseases - known as tauopathies. Little is known about their exact relationship to the different pathologies.
They a currently controversial because it's not known if they are causing disease, or simply a symptom of it.
Neurofibrillary tangles are formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate, or group, in an insoluble form. (These aggregations of hyperphosphorylated tau protein are also referred to as PHF, or “paired helical filaments”). The precise mechanism of tangle formation is not completely understood, and it is still controversial whether tangles are a primary causative factor in disease or play a more peripheral role.