Amyloid plaques have long been the target of Alzheimer’s-focused research, but a new study suggests it may be time to prioritize tau imaging instead.
That’s what researchers from the University of California San Francisco argued after using PET brain imaging to discover that tau protein tangles could predict the area of brain atrophy in Alzheimer’s patients at least a year ahead of time. The results, published Jan. 1 in Science Translational Medicine, suggest tau may be more of a primary force behind brain degeneration than amyloid protein.
“The match between the spread of tau and what happened to the brain in the following year was really striking,” Gil Rabinovici, MD, leader of the PET imaging program at UCSF’s Memory and Aging Center, said in a statement.
“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 been able to do with other imaging tools, and add to evidence that tau is a major driver of the disease,” he added.
Experts have long debated which type of misfolded protein clump common to Alzheimer’s patients is a primary cause of the disease: tau tangles or amyloid plaques. The latter has reigned supreme in arguments for years, with some even describing tau proteins as mere “tombstones” marking dying cells.
However, a new molecular imaging agent called flortaucipir—under FDA review—has changed what scientists can do. The injectable molecule binds to misfolded tau and releases a radioactive signal researchers can visualize via PET scans.
Rabinovici and colleagues recruited 32 patients with early stage Alzheimer’s who received a PET scan using two different tracers, one being flortaucipir. All participants also underwent MRIs to quantify their brain’s structural integrity.
They found that overall tau levels measured at the beginning of the study accurately predicted the degree of brain degeneration that would take place by the time patients underwent a follow up visit, which was on average 15 months later.
Localized patterns of tau accumulation were also more than 40% accurate at predicting future brain atrophy in that same location. Baseline amyloid PET scans, however, only did so in 3% of cases.
“Tau PET could be an extremely valuable precision medicine tool for future clinical trials,” Rabinovici said. “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.”