Tau protein tangles are a significant area of study in neurodegenerative diseases. They are abnormal clumps of protein that accumulate inside neurons and are a defining characteristic of several debilitating brain disorders. Understanding their development is a focus of neuroscience, as they are closely linked to the cognitive decline seen in these conditions.
The Normal Function of Tau Protein
In a healthy brain, tau protein is a productive component of the neuron’s internal structure. Neurons possess an internal support and transport system made of structures called microtubules, which function like a highway system for moving nutrients and molecules throughout the cell. Tau proteins act like railroad ties for these microtubule tracks, binding to them and providing stability.
This stabilizing function is particularly important in the long axons of neurons, where materials must travel significant distances. Different forms of tau protein contribute to the regulation of this cellular highway system. By modulating microtubule stability, tau ensures the neuron’s transport network remains functional for communication between brain cells.
The Formation of Neurofibrillary Tangles
The transition from a healthy tau protein to a destructive tangle begins with a chemical modification called hyperphosphorylation, where an excessive number of phosphate molecules attach to the protein. This process causes the tau protein to change its structure, detach from the microtubules, and leave the cellular highways unstable. The altered tau proteins become “sticky,” causing them to fold improperly and aggregate with other tau molecules.
These sticky proteins first form small clusters known as paired helical filaments because of their twisted, thread-like appearance. As more modified tau proteins join, these filaments grow into larger, insoluble masses inside the neuron called neurofibrillary tangles.
Impact of Tangles on Neuronal Health
The formation of neurofibrillary tangles has a two-pronged negative effect on a neuron. First, with tau proteins no longer stabilizing them, the microtubule transport system begins to disintegrate. This breakdown halts the movement of essential cargo, starving the neuron and disrupting its ability to communicate with other cells.
The physical accumulation of the tangles also creates a toxic environment, interfering with cellular processes and impairing systems that clear out damaged proteins. This combination of a collapsed transport network and internal toxicity leads to the death of the neuron. As more neurons die, the affected brain tissue begins to shrink in a process called atrophy.
Diseases Associated with Tau Tangles
The accumulation of neurofibrillary tangles is a pathological hallmark of neurodegenerative disorders known as “tauopathies.” Alzheimer’s disease is the most well-known of these conditions, where tangles tend to appear first in brain regions associated with memory, like the hippocampus, before spreading. The density and spread of these tangles correlate strongly with the severity of cognitive decline.
Another significant tauopathy is Chronic Traumatic Encephalopathy (CTE), which is associated with repeated head injuries and leads to mood swings and memory problems. Other primary tauopathies include Frontotemporal Dementia (FTD), affecting personality and language, and Progressive Supranuclear Palsy (PSP), which impacts movement and balance. While some of these diseases also involve other abnormal proteins, the presence of tau tangles is a common thread.
Detection and Therapeutic Strategies
For many years, tau tangles could only be definitively identified through post-mortem examination of brain tissue. Recent advancements in medical imaging, specifically Tau Positron Emission Tomography (PET), now allow scientists to visualize tau tangles in living individuals. This breakthrough enables earlier diagnosis and allows researchers to track the progression of tangle formation.
The ability to detect tangles has spurred the development of new therapeutic strategies. One approach involves developing drugs that inhibit the enzymes responsible for hyperphosphorylating tau. Another strategy uses immunotherapy to create antibodies designed to seek out and clear abnormal tau from the brain. Researchers are also exploring ways to stabilize microtubules to counteract the damage caused by tau detachment.