2020: New Groundbreaking Update on Alzheimer's Disease
University of California, San Francisco
January 2, 2020
Alzheimer 'tau' protein "tangles" as a harbinger for the location of future brain atrophy
PET scan of a human brain with Alzheimer's disease.
Brain imaging of pathological tau-protein "tangles" reliably predicts the location of future brain atrophy in Alzheimer's patients a year or more in advance, according to a new study by scientists at the UC San Francisco Memory and Aging Center. In contrast, the location of amyloid "plaques" was found to be of little utility in predicting how damage would unfold as the disease progressed. The plaques have been the focus of Alzheimer's research and drug development for decades.
According to the new research published January 1, 2020, "tau" drives brain degeneration in Alzheimer's disease more directly than amyloid protein, and also shows tau-based PET (positron emission tomography) brain imaging technology to accelerate Alzheimer's clinical trials and improve individualized patient care.
"There was a striking match between the spread of tau and what its impact on the brain in the following year". The "Tau PET imaging predicted not only how much atrophy we would see, but also where it would happen. These predictions were much more powerful than anything we've seen, and add to evidence that tau is a major driver of the disease."
Interest in Tau Growing as Amyloid-Based Therapies Stumble
Alzheimer's researchers have long debated the relative importance of amyloid plaques and tau tangles—two kinds of misfolded protein clusters seen in postmortem studies of patients' brains, both first identified by Alois Alzheimer in the early 20th century. For decades, the "amyloid camp" has dominated, leading to multiple high-profile efforts to slow Alzheimer's with amyloid-targeting drugs, all with disappointing or mixed results.
Tau protein, was once dismissed as simply a "tombstone" marking dying cells, and is currently being thought of as an important biological driver of the disease. In contrast, amyloid accumulates widely across the brain, sometimes even in people with no symptoms; autopsies of Alzheimer's patients have revealed that tau is concentrated precisely where brain atrophy is most severe, and in locations that help explain differences in patients' symptoms (in language-related areas vs. memory-related regions, for example).
"Still, just looking at postmortem brain tissue, it has been hard to prove that tau tangles cause brain degeneration and not the other way around. One of our group's key goals has been to develop non-invasive brain imaging tools that would let us see whether the location of tau buildup early in the disease predicts later brain degeneration."
Tau PET Scans Predict Locations of Future Brain Atrophy
Scientists recently developed an injectable molecule called flortaucipir—currently under review by the FDA—which binds to misfolded tau in the brain and emits a mild radioactive signal that can be picked up by PET scans.
One of the research showed that local patterns of tau buildup predicted subsequent atrophy in the same locations with more than 40 percent accuracy. In contrast, baseline amyloid-PET scans correctly predicted only 3 percent of future brain degeneration.
Notably, PET scans revealed that younger study participants had higher overall levels of tau in their brains, as well as a stronger link between baseline tau and subsequent brain atrophy, compared to older participants. This suggests that other factors—likely other abnormal proteins or vascular injuries—may play a larger role in late-onset Alzheimer's, the researchers say.
Ability to Predict Brain Atrophy a 'Valuable Precision Medicine Tool'
it is hoped that the tau-targeting drugs currently under study may provide clinical benefits to patients by blocking this key driver of neurodegeneration in the disease. At the same time, the ability to use tau PET to predict later brain degeneration could enable more personalized dementia care and speed ongoing clinical trials, the authors say.
"One of the first things people want to know when they hear a diagnosis of Alzheimer's disease is simply what the future holds for themselves or their loved ones. Will it be a long fading of memory, or a quick decline into dementia? How long will the patient be able to live independently? Will they lose the ability to speak or get around on their own?
Currently, we dind't have answer to these questions. "Now,however, for the first time, this tool could help us give our patients a sense of what to expect by revealing the biological process underlying their disease."
It is also believed that the ability to predict future brain atrophy based on tau PET imaging will allow Alzheimer's clinical trials to quickly assess whether an experimental treatment can alter the specific trajectory predicted for an individual patient. Such insights could make it possible to adjust dosage or switch to a different experimental compound if the first treatment is not affecting tau levels or altering a patient's predicted trajectory of brain atrophy.
Conclusion
"Tau PET could be an extremely valuable precision medicine tool for future clinical trials,". "The ability to sensitively track tau accumulation in living patients would for the first time let clinical researchers seek out treatments that can slow down or even prevent the specific pattern of brain atrophy predicted for each patient."
Source:
https://medicalxpress.com/news/2020-01-alzheimer-tau-protein-surpasses-amyloid.html
Comments
Post a Comment