A large international study found that healthy newborns have significantly higher levels of a key Alzheimer’s disease biomarker in their blood than adults diagnosed with the condition.
The findings raise questions about how tau functions differently across the human lifespan.
Researchers analyzed blood samples from more than 460 participants, including healthy newborns, premature infants, individuals with Alzheimer’s disease, and healthy people from adolescence to old age. They measured levels of phosphorylated tau217 (p-tau217), a biomarker associated with Alzheimer’s pathology.
In two independent newborn cohorts, average plasma p-tau217 levels were 10.19 pg/mL and 9.14 pg/mL. In comparison, patients with Alzheimer’s disease averaged 3.68 pg/mL. Healthy older adults, young adults, and teenagers all had levels below 2 pg/mL.
The results suggest that p-tau217 is not exclusive to disease but also plays a role in early brain development. In newborns, it may reflect intense neural activity linked to brain growth and microtubule regulation. Unlike in Alzheimer’s, where tau phosphorylation leads to aggregation and tangle formation, elevated levels in newborns do not appear pathological.
The study also tracked p-tau217 levels over time in premature infants born prior to 28 weeks’ gestation. Blood samples collected from birth through 133 days postnatal showed a gradual decline in levels. By 3 to 4 months following birth, p-tau217 concentrations dropped to levels similar to those of young adults.
These findings suggest that elevated tau phosphorylation at birth is part of a developmental process that diminishes as the brain matures. The mechanisms allowing newborns to tolerate high p-tau217 levels without developing tau-related pathology remain unclear.
The researchers also examined whether perinatal factors influenced p-tau217 levels. In one cohort, lower gestational age was associated with higher p-tau217, even after adjusting for other variables. No such associations were found with non-phosphorylated tau forms, suggesting a specific developmental role for the phosphorylated variant.
The study found no significant differences in p-tau217 levels among teenagers, young adults, and older adults. Similarly, there were no meaningful differences between the two newborn cohorts, indicating consistency across sites.
These findings point to a dual role for tau phosphorylation: critical during early neurodevelopment, but potentially pathological in later life. While p-tau217 remains a validated blood-based biomarker for Alzheimer’s disease, its high presence in infancy suggests a broader biological function.
Further research is needed to identify what regulates p-tau217 decline following birth and whether these natural protective processes can be adapted to prevent or treat neurodegenerative disease in adulthood.
Full disclosures can be found in the published study.
Source: Brain Communications