Tau protein is a naturally occurring component in the brain’s neurons. Normally, it performs several jobs that contribute to cell health, but certain changes can cause this protein to behave abnormally, leading it to accumulate and form clumps. This buildup is associated with a group of neurodegenerative conditions known as tau-related dementias. The changes in tau protein are often detectable in the brain decades before the first noticeable symptoms of cognitive decline, such as memory loss, appear.
The Role of Tau Protein in the Brain
Neurons possess a long extension called an axon. To maintain this structure and transport molecules, the cell relies on an internal support system of tube-like structures called microtubules. Tau protein’s primary function is to stabilize these microtubules, acting like railroad ties that hold train tracks in place, ensuring the efficient transport of nutrients and other cellular cargo.
The trouble begins when tau proteins undergo a chemical change and become hyperphosphorylated. This modification causes them to detach from the microtubules. Once free, these dysfunctional tau proteins stick to one another, forming insoluble, thread-like structures inside the neuron known as neurofibrillary tangles (NFTs). These tangles disrupt the cell’s transport system and are toxic, ultimately leading to the death of the neuron. As neurons die, communication pathways in the brain break down, causing the cognitive difficulties seen in dementia.
Types of Tau-Related Dementias
The diseases caused by the abnormal accumulation of tau are broadly classified as “tauopathies.” In primary tauopathies, the buildup of dysfunctional tau is the main pathological driver. This category includes several distinct disorders:
- Frontotemporal Dementia with tau pathology (FTD-tau), where accumulation is concentrated in the frontal and temporal lobes.
- Progressive Supranuclear Palsy (PSP), a condition marked by tau buildup in the brainstem and other areas controlling movement.
- Corticobasal Degeneration (CBD), where tau aggregates in various parts of the brain’s outer layer, or cortex.
- Pick’s disease, another disorder where abnormal tau is the central cause.
Alzheimer’s disease is considered a “secondary tauopathy.” While neurofibrillary tangles made of tau are a hallmark of Alzheimer’s, the disease is also characterized by the accumulation of another protein called amyloid-beta, which forms plaques outside of neurons. The buildup of amyloid-beta may appear first, triggering an increase in the formation of abnormal tau. This interaction between the two proteins contributes to the widespread neuronal damage seen in Alzheimer’s.
Symptoms and Disease Progression
The clinical presentation of primary tauopathies varies depending on which regions of the brain are most affected by tau accumulation. In many forms of Frontotemporal Dementia (FTD), the frontal lobes are heavily impacted, leading to noticeable changes in social conduct and executive function early in the disease.
Motor symptoms are a defining characteristic of other tauopathies. In Progressive Supranuclear Palsy (PSP), tau accumulation in the brainstem and basal ganglia leads to problems with balance, frequent falls, and difficulty with eye movements. Corticobasal Degeneration (CBD) often presents with motor difficulties, such as stiffness, clumsiness, or jerky movements in one limb.
Cognitive decline is a feature of all these disorders, but its nature can differ. While memory loss is a hallmark of Alzheimer’s disease, in primary tauopathies, other issues like language problems or difficulty with planning may be more pronounced. These diseases are progressive, meaning symptoms worsen over time as more neurons are damaged, leading to greater impairment in daily functioning.
Diagnosis and Current Research
Diagnosing a specific tau-related dementia relies on a thorough evaluation of a person’s symptoms and a neurological examination. Doctors look for the characteristic patterns of behavioral, motor, and cognitive changes associated with each disorder. Until recently, a definitive diagnosis could only be made by examining brain tissue after death to identify tau tangles.
Advances in medical imaging have introduced new tools. Specialized imaging, such as tau positron emission tomography (PET) scans, can now visualize and measure abnormal tau in the living brain. In 2020, the U.S. Food and Drug Administration approved the first imaging agent for this purpose, helping to confirm a diagnosis and track disease progression. Blood tests capable of detecting specific forms of abnormal tau are also becoming available.
Current research is focused on developing treatments that target the tau protein. One goal is to create drugs that prevent tau from clumping into tangles, known as anti-aggregation inhibitors. Another area is immunotherapy, which involves using the body’s immune system to clear abnormal tau from the brain. These approaches are still in investigative stages but represent a focused effort to slow or halt the progression of these diseases.