Newborns have elevated levels of an Alzheimer's biomarker

What do the brains of newborns and patients with Alzheimer’s disease have in common? According to a study led by the University of Gothenburg, both have elevated blood levels of a protein called phosphorylated tau, specifically a form called p-tau217.

This protein has been largely used as a diagnostic test for Alzheimer’s disease, with an increase in p-tau217 blood levels proposed to be driven by another process, namely aggregation of b-amyloid protein into amyloid plaques. Newborns do not have this type of pathological change, so increased plasma p-tau217 in newborns seems to reflect a completely different — and entirely healthy — mechanism.

In a large international study that involved Sweden, Spain and Australia, researchers analysed blood samples from over 400 individuals, including healthy newborns, premature infants, young adults, elderly adults, and people diagnosed with Alzheimer’s disease. They found that newborn babies had the highest levels of p-tau217 — even higher than those found in people with Alzheimer’s. These levels were particularly elevated in premature babies and started to decrease over the first few months of life, eventually settling to adult levels.

Previous research, largely based on animal models, had hinted at the role of phosphorylated tau in early brain development. This is understood to be the first time scientists have directly measured p-tau217 concentrations in the blood of human newborns, opening the door to a much clearer understanding of its developmental role.

In Alzheimer’s disease, p-tau217 is associated with tau aggregation into harmful clumps called tangles, believed to cause the breakdown of brain cells and subsequent cognitive decline. In newborns, this surge in tau appears to support healthy brain development, helping neurons grow and form new connections with other neurons, thereby shaping the structure of the young brain. And the earlier the birth, the higher the levels of this protein, suggesting a role in supporting rapid brain growth under challenging developmental conditions.

What’s perhaps most compelling about these findings, published in the journal Brain Communications, is the hint that our brains may once have had built-in protection against the damaging effects of tau, so that newborns can tolerate, and even benefit from, high levels of phosphorylated tau without triggering the kinds of damage seen in Alzheimer’s.

“We believe that understanding how this natural protection works — and why we lose it as we age — could offer a roadmap for new treatments,” said first author Fernando Gonzalez-Ortiz. “If we can learn how the newborn brain keeps tau in check, we might one day mimic those processes to slow or stop Alzheimer’s in its tracks.”

Plasma p-tau217 recently received US FDA approval for use in diagnosing Alzheimer’s disease, making it an increasingly important tool in clinical settings. The authors emphasise the need to understand the mechanism for the increase in p-tau217, especially for interpreting it as an outcome in clinical and epidemiological research and in drug development. Their study indicates that amyloid plaques may not be the main driver of increases in p-tau217.

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