Neurofibrillary tangles are abnormal clumps of protein that develop inside brain cells, or neurons. When these protein clumps form, they can disrupt the normal functioning of the brain, affecting how cells communicate and process information.
Understanding Neurofibrillary Tangles
Neurofibrillary tangles are made of an altered version of tau protein. Normally, tau helps stabilize microtubules, which are like internal railway tracks within neurons. These microtubules transport nutrients, vesicles, and other essential materials throughout the cell.
Normally, tau protein has phosphate molecules that help it bind to and stabilize microtubules. However, in tangle formation, tau undergoes hyperphosphorylation, where excessive phosphate molecules attach. This over-phosphorylation changes tau’s shape and function, causing it to detach from microtubules. Once detached, these abnormal tau proteins clump together, forming insoluble paired helical filaments. These filaments then twist and accumulate inside the neuron, eventually forming neurofibrillary tangles.
How Tangles Damage Brain Cells
The formation of neurofibrillary tangles directly impacts the health and function of brain cells. When tau proteins detach from microtubules due to hyperphosphorylation, the microtubule structures become unstable and can disintegrate. This collapse disrupts the neuron’s internal transport system, hindering the movement of vital substances within the cell.
Tangles also interfere with synaptic communication, the process by which neurons transmit signals. The accumulation of abnormal tau impairs neurons’ ability to send and receive messages efficiently, leading to breakdowns in neural networks. Tangles contribute to inflammation and oxidative stress within the brain. Such cellular distress can lead to neuron dysfunction and death, impairing brain function and causing cognitive decline.
Conditions Linked to Neurofibrillary Tangles
Neurofibrillary tangles are a hallmark of several neurodegenerative conditions, most notably Alzheimer’s disease. In Alzheimer’s, tangles are found alongside amyloid plaques, another abnormal protein deposit, and their presence increases as the disease progresses. Tangles are particularly prevalent in brain regions important for memory and cognition, such as the cerebral cortex and hippocampus.
Beyond Alzheimer’s disease, neurofibrillary tangles are also a defining characteristic of a group of disorders known as tauopathies. These conditions are specifically characterized by the accumulation of abnormal tau protein. Examples include certain forms of frontotemporal dementia (FTD), which affect personality, behavior, and language, and progressive supranuclear palsy (PSP), a disorder impacting movement, balance, and eye control. The presence and distribution of tangles can vary between these different tauopathies, contributing to the distinct symptoms observed in each condition.
Researching Treatments for Tangles
Current research efforts are focused on both detecting and treating diseases linked to neurofibrillary tangles. Diagnostic advancements include the development of imaging techniques, such as PET scans, that can visualize tau tangles in the living brain. Scientists are also exploring biomarkers in cerebrospinal fluid or blood that could indicate the presence and progression of tau pathology. These diagnostic tools help in earlier and more accurate identification of conditions involving tangles.
Therapeutic strategies being developed aim to address abnormal tau protein in several ways. Some approaches focus on reducing tau production within neurons, while others inhibit its aggregation into tangles. Researchers also investigate methods to enhance abnormal tau clearance from the brain or prevent its spread between neurons. These studies are developing future treatments for conditions where neurofibrillary tangles contribute to neurodegeneration.