Alzheimer's Disease Treatment, Diagnoses Could Be More Precise With Breakthrough Discovery Between Cognitive Decline and Misshapen Tau Proteins

An international team of researchers led by the School of Medicine at Case Western Reserve University made a significant breakthrough in why Alzheimer's disease rapidly progresses in some people that die within a couple of years.

Researchers found a relationship between strains of misshapen and fast-replicating tau proteins and the accelerated cognitive decline that has been reported in variations of Alzheimer's diseases. The team believes the findings could help lead to more precise diagnoses and target therapies in the near future.

Understanding the Relationship Between Misshaped Tau Proteins and Cognitive Decline

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Jiri Safar, the co-author of the study and a professor at the department of pathology, neurology, and neurosciences at Case Western Reserve School of Medicine, explains that for the first time, the team established the relationship between the tau protein's behavior in test tubes and the clinical duration of Alzheimer's disease in patients. He adds that the research says that Alzheimer's isn't a single disease in general. In fact, it is a spectrum of varying cases that have distinct biological drivers for its progression and should be handled by researchers and physicians as separate diseases.

Safar explains that the first step is to understand Alzheimer's then sort it out into its subsets and categories which is exactly where we are at now. He hopes that the research will help remove the public perception that patients diagnosed with Alzheimer's diseases likely decline slowly over eight to ten years; while ten to thirty percent have rapid progression of the disease which is 600,000 to 1.8 million US patients alone. He adds that now we can begin thinking about Alzheimer's the same way other clinicians handle malignancies such as pulmonary and breast cancer---- wherein different types of cancers have different prognoses and therapeutic strategies.

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Unraveling the Secrets of Tau Proteins

The next step now is to take the tools used in the study published in the journal Science Translational Medicine, titled "Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease," and translate them to clinical practices and identify patients at high risks for rapid progression of the disease to tailor fit treatments to the diagnosis.

The recent research follows the groundbreaking work of Safar involving prion proteins. Together with his colleagues, Safar discovered that when these prion proteins become misfolded, they replicate and damage the brain. The team used this concept and tools to investigate the mechanisms of misfolded proteins and apply them to tau proteins in Alzheimer's disease patients.

Scientists examined 40 brain samples from people who died of Alzheimer's disease that slowly lost about half of cognitive functions over the years and the rest declined rapidly and died in less than three years. The team found that in the rapidly progressing cases, the cores of tau proteins were shaped differently, which means they had varian structural organization. Furthermore, using the process the team developed previously, they found that the misfolded tau species, like prions, replicated rapidly in test tubes, reports NeuroScience.