Illustration of tau and neurofibrillary tangles in a neuron (nerve cell). The 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 presence of neurofibrillary tangles severely disrupts the brain?™s ability to function. Their accumulation is closely associated with cognitive decline, a hallmark of Alzheimer?™s disease. Although the process isn?™t fully understood, scientists believe that the buildup of amyloid-beta plaques outside neurons triggers the abnormal phosphorylation of tau proteins inside the cell, driving the formation of these destructive tangles.