Neurofibrillary tangles are abnormal clumps of protein found inside the brain’s nerve cells, known as neurons. These tangles are a distinguishing feature of several neurodegenerative conditions. Under a microscope, they appear as twisted, insoluble fibers that disrupt brain cell function. Their presence indicates the progression of certain brain disorders.
The Building Blocks of Tangles
Neurofibrillary tangles are primarily composed of a protein called tau. In a healthy brain, tau protein stabilizes microtubules, which act like internal railway tracks within neurons, transporting nutrients and molecules throughout the cell.
Tangle formation begins when tau protein undergoes an abnormal chemical change called hyperphosphorylation, where excessive phosphate groups attach to it. When tau becomes hyperphosphorylated, it detaches from the microtubules, causing them to become unstable and eventually disintegrate. The unbound tau proteins then clump together, forming larger, twisted neurofibrillary tangles. This aggregation represents a significant departure from tau’s healthy role in maintaining neuronal structure and transport.
How Tangles Impact Brain Function
The presence of neurofibrillary tangles within neurons has serious consequences for brain function. As tau aggregates, it disrupts the neuron’s internal transport system. This disruption impedes the flow of essential nutrients and molecules, leading to cellular dysfunction and nerve cell death, a process called neurodegeneration.
The damage caused by tangles extends beyond individual cells, impairing communication between neurons. This breakdown in synaptic communication contributes to cognitive decline and memory problems. An increase in neurofibrillary tangle burden is associated with the severity of cognitive impairment.
Neurofibrillary Tangles and Disease
Neurofibrillary tangles are a prominent feature in several neurodegenerative diseases, with Alzheimer’s disease being the most recognized. In Alzheimer’s disease, these tangles are considered a hallmark pathology, accumulating in the cerebral cortex and hippocampus, brain regions involved in memory. The number of neurofibrillary tangles often correlates with the severity of dementia in Alzheimer’s patients, suggesting their direct involvement in neuronal dysfunction and the progression of symptoms such as memory loss, impaired judgment, and changes in personality.
While most commonly associated with Alzheimer’s, neurofibrillary tangles are also found in a group of disorders collectively known as tauopathies. These conditions primarily involve the abnormal accumulation of tau protein. Examples of other tauopathies include progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Chronic traumatic encephalopathy (CTE), a condition often seen in individuals with a history of head injuries, also features tau tangle pathology. The presence of tangles in these diseases underscores the impact of tau protein dysfunction on brain health, although the patterns and types of tau aggregates can vary between conditions.
Distinguishing Tangles from Other Brain Changes
When discussing brain changes in neurodegenerative diseases, neurofibrillary tangles are often mentioned alongside amyloid plaques. These two pathologies are distinct yet frequently coexist, particularly in Alzheimer’s disease. Amyloid plaques are dense, sticky clumps of a different protein called beta-amyloid, which accumulate in the spaces between neurons, outside the cells.
In contrast, neurofibrillary tangles are formed inside neurons and are made of abnormal tau protein. While both are considered pathological hallmarks of Alzheimer’s disease, they play different roles in the disease process. Amyloid plaques are thought to disrupt communication between brain cells, while tangles interfere with the internal transport system and structural integrity of individual neurons. Although the precise mechanisms linking the formation of plaques and tangles are still being investigated, research suggests an interplay between these two protein abnormalities in the progression of Alzheimer’s.