In a study published in Science Translational Medicine, a new study by scientists at the center for memory and aging at the University of California, San Francisco (UCSF), shows that brain imaging of pathological tau tangles can reliably predict the location of brain shrinkage in Alzheimer’s patients a year or more in the future. In contrast, the location of amyloid plaques, which have been the focus of disease research and drug development for decades, has been found to have little effect.
Figure 1 Voxelwise spatial correlations between baseline PET patterns and the topography of subsequent atrophy
In healthy people, a protein called tau is important for supporting the internal structure of brain cells. However, in patients with Alzheimer’s disease, chemical changes occur that cause protein to form tangles that destroy cells. This tangling was previously thought to be related to the loss of brain cells.
The findings have led researchers to increasingly realize that tau causes Alzheimer’s brain degradation more directly than amyloid. They also demonstrated the potential of their recently developed tau-based positron emission tomography (PET) brain imaging technology to accelerate clinical trials in Alzheimer’s and improve patient-specific care.
“The matching between the spread of tau and changes in the brain the following year is truly shocking,” said study author Gil D. Rabinovici, a neuroscientist at UCSF and Lawrence Berkeley National Laboratory. “We used PET imaging to study the brains of 32 people with early Alzheimer’s symptoms between the ages of 49 and 83. We tracked the degree of tau tangle in the brain, and found that the level of this protein not only predicts how much atrophy will occur in the brain later but also the location of the atrophy. These predictions are much stronger than anything we do with other imaging tools, and further prove that tau is a major driver of the disease. ”
Although previous studies have shown that brain atrophy is more strongly associated with tau protein tangles than β-amyloid, the team says the discovery is still surprising. La Joie said: “We were surprised to find that tau can not only predict the overall degree of atrophy but also accurately predict the location of atrophy in individual patients.” This study has limitations, including that PET scans can only indirectly measure tau and beta-amyloid levels, and tracking substances may not just bind to these proteins. This relatively small study further demonstrates that tau protein may cause brain cell death, and explains why tau protein worsens as it spreads throughout the brain.
This result adds hope to the research team that the UCSF Memory and Aging Center and other institutions are currently studying tau-targeted drugs that may provide clinical benefits to patients by blocking key drivers of neurodegeneration in this disease. At the same time, researchers said that using tau’s PET to predict future brain degeneration could enable more personalized care for dementia and speed up ongoing clinical trials.
Currently, some drugs for tau protein tangles are undergoing clinical trials, including some drugs designed to interfere with the production of tau protein in the brain or its transmission between cells. The results of this study suggest that imaging techniques may prove valuable in choosing which patients to test for such drugs and monitoring their effectiveness.
La Joie, R., Visani, A. V., Baker, S. L., Brown, J. A., Bourakova, V., Cha, J., … & Lesman-Segev, O. H. (2020). Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET. Science Translational Medicine, 12(524).