Tau Protein and Alzheimer’s Disease: What’s the Connection?

Tau proteins in the brains of people with Alzheimer’s disease are misfolded and abnormally shaped. The normal tau protein forms part of a structure called a microtubule. One of the functions of the microtubule is to help transport nutrients and other important substances from one part of the nerve cell to another. Learn more about the connection between tau and Alzheimer’s disease.

What is Tau?

The tau protein is predominantly found in brain cells (neurons). Among tau’s multiple functions in healthy brain cells, a very important one is stabilization of the internal microtubules. Tau is a small protein with a short name but a large reputation because of its association with multiple brain diseases.

When mice are genetically designed to lack tau protein, their brain cells do not function properly, and tau dysfunction has been identified in a number of very severe human brain diseases.

Video: How Alzheimer’s Changes the Brain

Brain Diseases Associated with Tau

Alzheimer’s disease is well known to feature neurofibrillary tangles that are composed of modified tau protein. Some other serious brain diseases associated with abnormal tau protein are chronic traumatic encephalopathy, Pick disease, frontotemporal dementia with parkinsonism-17 (FTDP-17), progressive supranuclear Palsy (PSP), and corticobasal degeneration (CBD). Although each of these forms of dementia are different, they are all severe and progressive.

Different Forms of Tau

The abnormal tau proteins found in these neurodegenerative diseases are not identical, although they are related. A genetically mutant form of tau can wreak havoc and does so in FTDP-17. The other diseases mentioned feature variants of tau protein created by splicing together tau’s smaller components in different patterns to create the six different human forms.

Then, after tau has been created from DNA, chemical activities in the brain further modify it in several ways. These chemical alterations of tau change its properties. No longer fit to carry out its usual job, it takes on characteristics that are potentially very damaging. This form of tau no longer sticks together in the same way. Instead, the fabric of connected tau proteins comes apart and reassembles in a disorganized, messy tangle that accumulates in brain cells and is not effectively disposed of through the cell’s usual ways of removing “trash.” Besides the microtubular form, which is composed of many tau molecules, tau also exists in smaller versions, called oligomers, which are made up of a few tau proteins. The smaller forms of tau circulate among the neurons, interfering with cellular function. They are found in brains that are developing AD decades before the disease blossoms clinically.

What Causes Tau Buildup?

Scientists have long pointed to the importance of tau in AD because of evidence linking the spread of tau with disease progression. The accumulation of beta amyloid in the brain of a person with AD is largely completed at an earlier clinical stage known as mild neurocognitive disorder. However, tau accumulation continues throughout the course of the disease. Beginning in the parts of the brain called the entorhinal cortex and hippocampus, brain tau continues to accumulate as AD progresses. Recent evidence suggests that tau spreads through the brain by means of oligomer “seeds” that travel across a structure, called a synapse, which allows a nerve cell to pass an electrical or chemical signal to another nerve cell. The total amount of abnormal tau in the AD brain is linked to disease stage and severity.

Medical Tests for Tau

Tau accumulation and neurofibrillary tangles, like amyloid plaques, are not yet measurable with an available blood test, although research is ongoing. Moreover, the conditions cannot be visualized on a CT or MRI scan. However, PET scanning can identify and measure the amount of accumulation for either of these disease-related proteins. In the case of amyloid, the PET scan won’t identify the stage of dementia because of amyloid’s early accumulation. Tau PET scans, on the other hand, may in the future provide a biomarker measurement that will meaningfully indicate disease progression. Amyloid PET scan tracers, which are already FDA-approved, are often used now to screen candidates for AD clinical trials. They identify the presence of disease but are not useful for measuring disease progression. Tau PET scan tracers have been developed and evidence supports tau PET scanning as a biomarker that reflects the stage of neurodegeneration associated with Alzheimer’s Disease. The first of the tau PET tracers to be approved by the US FDA is F-18 flortaucipir. Many new AD clinical trials are including tau PET scans as a potential biomarker of disease severity.