The tau protein linked to Alzheimer's is also present in the brains of newborns. Much more than in patients.

The protein phospho-tau217 (pTau217), currently considered one of the most useful markers for predicting dementia and used in the very recent blood tests for Alzheimer's disease (the first was approved in the US last May), has been found in very high concentrations in newborns, particularly premature infants. Much higher than in people diagnosed with Alzheimer's disease.

The study and the levels of p-tau217 protein in newborns

The discovery—which appears to challenge a decades-old dogma—is the work of an international team of scientists led by the University of Gothenburg in Sweden, who analyzed blood samples from over 400 individuals, including healthy newborns (preterm and otherwise), young adults, seniors, and patients with Alzheimer's disease. The data, published in Brain Communication, reveal that perfectly healthy newborns have higher concentrations of p-tau217 than anyone else in the population tested. Furthermore, the more premature the baby, the higher the concentration. In second place in this ranking are newborns conceived at term. Levels then drop sharply during the first months of life and remain very low, only to rise again in people with Alzheimer's disease, where, however, they never reach the concentration observed in newborns (they remain about three times lower, on average).

P-tau217, no longer just a marker of Alzheimer's

p-tau217 is the "altered" version of the tau protein: in people with dementia, it has been observed to form "tangles" within the brain and compromise function, leading to memory loss typical of these conditions. "The new findings tell us that one of the most sought-after brain cell 'killers' in patients with dementia is present under perfectly normal conditions in newborns. This actually doesn't surprise neuroscientists who have been studying p-tau for years," Paolo Maria Rossini, Director of the Department of Neuroscience and Neurorehabilitation at the IRCCS San Raffaele in Rome, told Salute. "We already knew that this protein is important for organizing the internal structure of neurons, which are highly complex cells. Therefore, it was expected that higher concentrations would be found in the developing brain, as already shown in studies on animals and fetal neurons." The same, explains the expert, applies to amyloid, a protein well known for its role in Alzheimer's (its aggregates damage communication between neurons and lead to their death), but which also performs an immune function.

Why is studying important?

"Evidently," Rossini emphasizes, "these substances are two-faced: they are partly 'bad' and partly 'good.' It's clear that the newborn brain has protective mechanisms that allow it to maximize the good functions and inhibit the bad ones." Not only that: the newborn brain is also capable, at a certain point in its development, of eliminating the p-tau217 it no longer needs and keeping its levels under control. How does it do this?

There's one final point: for years, it was thought that p-tau217 increases only after amyloid begins to accumulate in the brain, triggering the process that leads to dementia. But newborns don't show amyloid plaques, suggesting that the two proteins operate independently and that other biological processes regulate tau. "These are the most intriguing aspects of the study, beyond the fact that it confirms a hypothesis. If we find the answers to these questions, we could gain important information for developing innovative drugs." These answers will need to be sought by studying the brains of newborns and could reveal entirely new ways to prevent or treat Alzheimer's and dementia.

Doubts about the predictive capacity of tests in healthy young people

Finally, a comment should be made on the predictive value of this and other so-called markers, both plasma and CSF, Rossini concludes: "Having altered levels of amyloid and tau does not accurately predict the risk of developing dementia in relatively young subjects. This is confirmed by the results of the Italian Interceptor study and the very recent publication in Nature Medicine of a study from the Swedish Karolinska Institute, which features the names of several Italian researchers, including Giulia Grande and Laura Fratiglioni, demonstrating that the predictive value of dementia risk based on plasma p-tau levels is no higher than a coin toss."