P-tau217 in Early Disease Detection: True Biomarker Value or Diagnostic Mirage?
DOI:
https://doi.org/10.64261/ng288b81Keywords:
p-tau217, Alzheimer’s disease, neonatal brain, biomarkers, tau pathology, synaptogenesis, neurodevelopment, diagnosticsAbstract
Introduction: Phosphorylated tau (p-tau217) at the threonine 217 site is considered to be one of the most sensitive and specific biomarkers of early Alzheimer’s disease (AD). But it is facing new evidence showing that p-tau217 is present in unexpectedly high levels in the brains of neonatal brains, which is problematic with regard to its diagnostic specificity in different age groups.
Methods: The analysis of the literature through a narrative was performed in PubMed/MEDLINE, Scopus, and Web of Science (2020-2025).
Results: The results suggest that in the neonatal brains the levels of p-tau 217 are equal or higher than in the AD brains without amyloid- 217 deposition, neurofibrillary tangles or neurodegeneration. During early stages, non-aggregative, transient, and reversible, p-tau217 is required to facilitate critical processes including axonal development, synaptogenesis, synaptic pruning and neural plasticity.
Discussion: These findings underline that p-tau217 is a developmental and disease-related form of tau. Use of fixed diagnostic thresholds without age contextualization can produce a greater risk of false-positive interpretation especially among pediatric or asymptomatic groups.
Conclusion: p-tau217 is not a purely pathological biomarker to consider. It is important to have age-adjusted reference ranges, multimodal diagnostic frameworks, and clinical correlation in order to interpret them accurately. The identification of the physiological role of p-tau217 in developing the human brain will be more diagnostic and less misclassified in biomarker-based neurology.
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