Tau may better predict Alzheimer's effect on brain than amyloid

Tau protein is a superior predictor than amyloid protein of the effect of Alzheimer’s disease on a patient’s brain, according to results of a prospective observational study published in Science Translational Medicine.

“For each patient, the amount of brain shrinkage and the regional distribution of atrophy followed the amount and the distribution of tau pathology,” Renaud La Joie, of the department of neurology, at the University of California, San Francisco’s Weill Institute for Neurosciences, told Healio Psychiatry. “Brain regions that showed the most degeneration over the course of the study were the regions harboring the most tau pathology at baseline. Our data therefore strongly suggest that tau is upstream of brain atrophy in the disease course and is likely the driver of brain degeneration.”

According to La Joie and colleagues, previous research has offered conflicting findings on the importance of amyloid plaques and tau tangles — two forms of misfolded protein clusters — regarding Alzheimer’s disease development. Much of this research elevated amyloid as the central driver, but the present study compared the predictive capabilities of beta-amyloid with tau-positron emission tomography (PET) radiotracers for subsequent brain atrophy. To test these, the researchers used longitudinal MRI acquired at the time of PET and 15 months later among a group of 32 patients at early symptomatic Alzheimer’s disease stages.

Using quantitative analyses, they found that the global intensity of beta-amyloid-PET signal did not predict the rate of subsequent atrophy, but this signal intensity was predictive for tau-PET, independent of baseline cortical thickness. Further, they reported that specific distribution of tau-PET signal strongly indicated the topography of future atrophy at the single patient level. In younger patients, the relationship between baseline tau-PET and subsequent atrophy was particularly strong.

“These findings don’t mean that amyloid pathology is not deleterious somehow, but they do support the idea that tau pathology would be a very relevant drug target to prevent brain damage,” La Joie said. “Based on our study, and on the fact that brain shrinkage is tightly associated with cognitive function, it is reasonable to expect that the amount and topography of tau-PET will be able to indicate future cognitive changes, but we will have to test this in order to make this technology even more relevant to clinical practice.” – by Joe Gramigna

Disclosures: La Joie reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.