In these affected, malfunctioning neurons, tau proteins – which normally attach to structures called microtubules – are instead detaching and clumping together abnormally. These aggregating clumps are known as neurofibrillary tangles (NFTs). As more and more tau proteins are drawn into these tangles, there are fewer left to support the microtubules. This shortage leads to a harmful cycle where cells function poorly and eventually die.

The formation of neurofibrillary tangles greatly disrupts neuronal function. It is closely linked with a gradual decline in cognitive abilities and is one of the key pathological characteristics of Alzheimer's disease.

While not completely understood, it is thought that the accumulation of amyloid-beta plaques outside the neurons initiates abnormal phosphorylation of tau protein inside the neuron.

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