Tau Protein: A Double-Edged Sword in Alzheimer's
Over the past few years, researchers have made strides in understanding how Alzheimer's disease (AD) develops over time by using positron emission tomography (PET) scans to study the brains of people who have this devastating condition. Until recently, most of the focus of this research has been on using PET scans to detect a protein, beta-amyloid, that is one of the hallmarks of AD.
Thanks to new developments in imaging technology, however, researchers are now able to use PET scans to search for a different protein known as tau. Although tau is essential for normal cell functioning, it can also become dysfunctional and cause the formation of neurofibrillary tangles, abnormal twisted threads found within the brain nerve cells, called neurons, of almost all people with AD.
The results of early studies using PET scans to detect tau are helping to reshape ideas about AD and provide a greater understanding of the progression of neurological changes that lead to the gradual loss of memory and other cognitive abilities.
To produce a PET scan of the brain, a radioactive material known as a tracer is injected into the patient's vein. Tracers are designed to bind to specific targeted proteins in the body. Brain PET scans can detect where the tracers accumulate in the brain.
In a groundbreaking study published in 2016 in JAMA Neurology, researchers used PET scans with tau tracers to examine the brains of 59 men and women, whose average age was 74. Some had AD, but the study also included individuals with normal cognition.
This study demonstrated that a PET scan using tau tracers was able to distinguish people with AD from those who didn't have the disease. Specifically, study participants with AD had high levels of tau in the hippocampus and the cerebral cortex—brain regions that play critical roles in forming and storing memories. The same was not true for people with normal cognition.
However, the presence of either amyloid or tau alone did not appear to be sufficient to cause cognitive impairment: Both proteins had to be present for a person to have evidence of atrophy, or shrinkage, in the hippocampus—the first area affected by Alzheimer's. The authors of this study hypothesize that amyloid transforms tau into a more toxic version of itself, causing it to destroy greater numbers of neurons (brain cells) and synapses (connections between neurons).
Findings from a 2017 investigation published in the journal Brain support the idea that amyloid and tau must interact to cause AD. Researchers recruited 217 participants, including 95 people with mild cognitive impairment (MCI) and 48 individuals who had been diagnosed as possibly or probably having AD; the remainder were a mix of young and older people with no cognitive symptoms. All participants underwent PET scans with tracers for amyloid and tau. Among individuals whose PET scans were positive for amyloid, those who also had high levels of tau were significantly more likely than those with few or no tau deposits to have AD or MCI. Moreover, there was a direct correlation between tau levels and cognition in amyloid-positive participants: The more tau a person had, the worse his or her cognitive impairment tended to be.
Investigators don't fully understand how tau proteins migrate through the brain; animal research suggests that they may move from one neuron to another across synapses (small areas on neurons that release chemical messages). Amyloid may trigger tau to spread faster, leading to the degeneration that causes memory loss, cloudy thinking, and other AD symptoms. Additional research is needed to corroborate or disprove this hypothesis.