Healthy infants found to have high blood levels of p-tau217, a key Alzheimer’s biomarker, in new JAMA research

Researchers reported in JAMA on Thursday that healthy newborns had unexpectedly high blood levels of phosphorylated tau 217 (p-tau217), a biomarker commonly linked to Alzheimer’s disease, based on analysis of more than 460 participants across multiple age groups. The study suggested that elevated p-tau217 in infants may reflect a normal physiological role in early development rather than disease, according to the published findings.

The study analyzed blood samples from 462 participants across multiple age groups, including two independent cohorts of healthy newborns, premature infants, teenagers, young adults, older adults, and individuals diagnosed with Alzheimer’s disease, according to the peer-reviewed article published in Brain Communications. Researchers reported that average plasma levels of phosphorylated tau 217 (p-tau217) in healthy newborns were approximately 10 picograms per milliliter (pg/mL), nearly three times higher than levels measured in patients with Alzheimer’s disease and more than five times greater than those observed in teenagers, young adults, and older adults, according to the JAMA summary and secondary reporting by Scientific American.

The study used a high-sensitivity UGOT p-tau217 assay to quantify the biomarker, which is typically associated with amyloid beta pathology and neurodegeneration in Alzheimer’s disease.

However, the elevated levels found in healthy infants suggest a normal physiological role for p-tau217 in early brain development rather than a disease process, the authors concluded. The research highlighted that tau phosphorylation supports microtubule dynamics, axonal transport, neuroplasticity, and neurite outgrowth, functions critical to fetal and neonatal brain maturation.

In examining premature infants born before 28 weeks of gestation, the researchers found that many had even higher p-tau217 blood levels than full-term newborns. Longitudinal measurements indicated that p-tau217 concentrations declined over time postnatally, reaching levels comparable to healthy young adults by approximately 20 weeks after birth, according to the Brain Communications paper and the study’s reporting summary. This postnatal decline further supports the interpretation of p-tau217 as a developmental biomarker during early life stages.

The Alzheimer’s disease cohort included individuals with clinically confirmed Alzheimer’s dementia and mild cognitive impairment of the Alzheimer’s type, diagnosed through lumbar puncture-based biomarker testing and cognitive evaluations, according to the study’s methodology. While these patients exhibited elevated p-tau217 levels relative to healthy adults, their concentrations were less than half those measured in the newborn cohorts. This contrast underscores the biomarker’s dual role, appearing in both normal neurodevelopment and neurodegeneration but within distinct biological contexts.

Healthy adolescent and adult control participants reported no cognitive difficulties and demonstrated no impairment on cognitive testing, serving as a baseline for comparison. Their plasma p-tau217 levels consistently measured below 2 pg/mL, significantly lower than levels seen in newborns and Alzheimer’s disease patients. The research team emphasized that the elevated p-tau217 in infants is not indicative of neurodegenerative disease but rather reflects active neurodevelopmental processes.

The multicenter study, conducted across several institutions, was detailed in the article titled “plasma phosphorylated-tau217 in newborns and Alzheimer’s disease,” published in Brain Communications. The findings were also highlighted in a medical news item in JAMA on June 6, 2024. The research contributes to understanding the physiological functions of tau phosphorylation during early human development and informs the interpretation of p-tau217 in clinical diagnostics, where it is increasingly used as a blood-based biomarker for Alzheimer’s disease, including in FDA-approved testing workflows.

Researchers noted that the infant brain may possess protective mechanisms preventing the pathological aggregation of tau proteins seen in Alzheimer’s disease later in life. The study’s insights may influence future biomarker research and the clinical application of p-tau217 measurements across the lifespan.