Teams of scientists working on Alzheimer’s have long debated the relative importance of amyloid plaques and tangles of Tau, two types of poorly folded protein aggregates, seen in post-mortem studies of patients’ brains. For decades, the “amyloid camp has dominated”, leading to many candidates trying to slow the progression of the disease by targeting the amyloid, with disappointing or mixed results.
Today, more teams are “looking” at the Tau protein, once considered a simple tag to mark dying cells, and investigating whether Tau could be a biological driver of the disease. Unlike amyloid, which accumulates widely in the brain, sometimes even in people without symptoms, autopsies of Alzheimer’s patients reveal that Tau is concentrated precisely where the brain atrophy is most marked, and in areas that explain the differences in cognitive symptoms between patients.
This new study supports Tau’s major responsibility as well as the idea that brain imaging targeted at tangles of pathological tau proteins can reliably predict the location of future cerebral atrophy in Alzheimer’s patients. a year or more in advance. On the contrary, therefore, amyloid plaques, little predictive of the progression of the disease.
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Tau, the protein most directly responsible for brain degeneration
Tau, a major “driver” factor of the disease: the study supports the current current of research, more favorable to a major and direct responsibility for Tau in the cerebral degeneration associated with Alzheimer’s disease and demonstrates, at the same time the potential of PETscan recently developed to detect tangles of Tau . Indeed, this work reveals that the spread of Tau is closely and “strikingly” linked to cognitive evolution the following year, comments the main author, Dr. Gil Rabinovici, neurologist and head of the imaging program. PETscan at the UCSF Center for Memory and Aging. “Tau-PET imagery not only predicts the amount of atrophy but also the site of the brain where it will occur. These predictions are far more powerful than anything we have been able to obtain using other imaging techniques, and add to the evidence that Tau is a major “driver” of the disease.
More precise brain imaging technology: scientists have developed an injectable molecule called flortaucipir – currently under investigation by the US agency FDA – which binds to the improperly folded Tau protein in the brain and emits a soft radioactive signal that can be picked up by imaging. This new kind of PETscan studies the distribution of Tau tangles in the brain.
This study tested whether the Tau levels detected in 32 Alzheimer’s patients predicted future brain degeneration. Participants also had MRIs to measure the structural integrity of their brains, both at the start of the study and again during follow-up visits, 1 and 2 years later. Analysis shows that:
- the overall levels of Tau in the brain at the start of the study predict well the severity of the degeneration as assessed during subsequent follow-up visits;
- local Tau accumulation models predict sites of atrophy with 40% accuracy;
- however, scans of amyloid plaques correctly predict only 3% of future brain degeneration.
- younger participants have higher overall Tau levels and imagery in these patients reveals a stronger link between tangles detected and subsequent brain atrophy: this suggests that other factors, perhaps other abnormal proteins or vascular damage could also play a role in the progression of Alzheimer’s disease.
In conclusion, the imaging technique, which predicts the sites of future brain atrophy in patients, will not only speed up clinical trials on Alzheimer’s disease but also provide better personalized care to patients . The results also confirm the hope that the drugs targeting Tau, currently under study, could offer clinical benefits to patients by blocking neurodegeneration. Finally, the Tau-PET tool will, for the first time, allow doctors to give patients an idea of what they can expect by revealing the biological process behind their disease.
No one doubts that amyloid plays a role in Alzheimer’s disease, conclude the researchers, but more and more data suggest that Tau is really at the origin of the disease. ” Tau-PET can become an extremely valuable precision medicine tool for future clinical trials, but also for personalized monitoring and treatment of patients living with the disease “.
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