Summary: A new multicentre study finds that newborn infants and people with Alzheimer’s disease share unusually high blood levels of the same phosphorylated tau protein, p-tau217. In Alzheimer’s, p-tau217 is a well-established marker of neurodegeneration. In newborns, however, the same protein appears to play a healthy, developmental role: levels are highest at birth—particularly in premature infants—and decline during the first months of life. Understanding how the newborn brain tolerates and uses high p-tau217 could point to new strategies for preventing or treating Alzheimer’s.
The research suggests that similar molecular signals can serve very different biological purposes depending on age and context. The study measured plasma p-tau217 across a broad age range and clinical groups, revealing a striking developmental peak that contrasts with the protein’s pathological role in older adults with Alzheimer’s disease.
Key facts:
- Shared biomarker: Newborns and people with Alzheimer’s both show elevated blood levels of p-tau217.
- Distinct mechanisms: In infants, the rise in p-tau217 appears linked to healthy brain maturation; in Alzheimer’s it marks pathological tau aggregation.
- Therapeutic potential: Investigating how infants avoid tau-related damage may reveal protective mechanisms that could be targeted in Alzheimer’s research.
Source: University of Gothenburg
What do newborn brains and Alzheimer’s-affected brains have in common?
Researchers at the University of Gothenburg, led by Fernando Gonzalez-Ortiz and Professor Kaj Blennow, measured plasma p-tau217 levels in a large international cohort. The study included over 400 participants from Sweden, Spain and Australia: healthy newborns, premature infants, young adults, older adults, and people diagnosed with Alzheimer’s disease. The team found that p-tau217 concentrations were unexpectedly high at birth—higher even than in some patients with Alzheimer’s—and were especially elevated in premature infants.
Previous experimental work had suggested that phosphorylated tau contributes to microtubule dynamics and neuronal growth during fetal and early postnatal development. This study is the first to directly quantify p-tau217 in human newborn blood, confirming a developmental peak and documenting a rapid decline across the first months of life toward adult levels.
Importantly, the study distinguishes two very different biological contexts for elevated p-tau217. In Alzheimer’s disease, p-tau217 correlates with tau aggregation into neurofibrillary tangles—protein clumps implicated in neuronal dysfunction and cognitive decline. In contrast, the neonatal surge in p-tau217 seems to support synapse formation and circuit wiring, essential processes for building a functional brain.
The researchers also found a clear relationship between gestational age and p-tau217 concentration: the earlier the birth, the higher the p-tau217 level. Levels in preterm infants fell over time in longitudinal samples, approaching the concentrations seen in young adults as development progressed. This pattern suggests p-tau217 helps accommodate the rapid and high-demand phase of brain growth that follows preterm birth.
Implications for Alzheimer’s research and therapy
One of the most intriguing implications is that newborns may possess regulatory mechanisms that permit high phosphorylated-tau without triggering aggregation and neurotoxicity. Uncovering how the infant brain prevents tau aggregation or mitigates its harmful effects could point to protective pathways that are lost with aging. “Understanding how this natural protection works—and why we lose it as we age—could offer a roadmap for new treatments,” says 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.”
Plasma p-tau217 has recently gained approval for clinical use in Alzheimer’s diagnostics, increasing its relevance for both clinical practice and research. The study’s authors emphasize that interpreting p-tau217 as a biomarker requires knowledge of the underlying mechanisms that drive its increase in different contexts. Their findings suggest that amyloid plaque accumulation may not be the sole driver of p-tau217 elevation, at least in early life.
About this genetics, Alzheimer’s disease, and neurodevelopment research news
Author: Margareta G. Kubista
Source: University of Gothenburg
Contact: Margareta G. Kubista – University of Gothenburg
Image: The image is credited to Neuroscience News
Original research (open access):
“The potential dual role of tau phosphorylation: Plasma p-tau217 in newborns and Alzheimer’s disease” by Fernando Gonzalez-Ortiz et al., published in Brain Communications.
Abstract
The potential dual role of tau phosphorylation: Plasma p-tau217 in newborns and Alzheimer’s disease
Tau phosphorylation plays essential roles in both normal brain physiology and neurodegenerative pathology. During fetal and early postnatal development, phosphorylation of tau supports microtubule dynamics and neuroplasticity; in Alzheimer’s disease (AD), it contributes to pathological tau aggregation and tangle formation.
In this multicentre study (n = 462), plasma p-tau217 was measured in healthy newborns, premature infants, patients with AD, and healthy controls spanning multiple age groups. Newborns exhibited significantly higher plasma p-tau217 concentrations than healthy individuals of any age and, at times, higher than levels observed in patients with AD. In newborns, p-tau217 levels were inversely correlated with gestational age. Longitudinal sampling in preterm infants showed a decline in p-tau217 over the first months of life toward levels typical of young adults. In older individuals, elevated plasma p-tau217 was associated with AD pathology.
These results reinforce the crucial role of tau phosphorylation in early brain development while highlighting that the same molecular modification becomes pathological in AD. The transient, high levels of p-tau217 at birth and their subsequent clearance suggest distinct regulatory mechanisms in early life that prevent tau aggregation. Further studies are needed to elucidate shared and divergent mechanisms of tau phosphorylation in newborn development and Alzheimer’s disease.