Phosphorylated tau 217 in young adults with Down syndrome and Down syndrome regression disorder

Topic: Brain proteins, microglia and lab models

Abstract Background Down syndrome regression disorder (DSRD) causes a rapid loss of cognitive, behavioral, and daily living skills, usually in adolescents and young adults with Down syndrome. Because people with Down syndrome have a high lifetime risk of Alzheimer’s disease, we examined whether DSRD is associated with an Alzheimer-related pattern of tau pathology. Methods In this prospective, single-center study, we measured plasma phosphorylated tau-217 (p-tau217), a blood marker of Alzheimer pathology, in 132 participants: 48 with DSRD, 39 with Down syndrome without regression (DSwR), and 45 neurodevelopmental controls. We compared p-tau217 concentrations across groups and examined relationships with demographic factors, medical conditions, treatment status, and diagnostic test abnormalities. Results Median p-tau217 concentrations were similar in the DSRD (0.082 pg/mL), DSwR (0.084 pg/mL), and neurodevelopmental control (0.080 pg/mL) groups (overall comparison, p = 0.57). Pairwise comparisons and models accounting for demographic and clinical factors also showed no statistically significant group differences. Among participants with DSRD, p-tau217 was not associated with treatment status or abnormalities on brain-wave testing, neuroimaging, or cerebrospinal fluid analysis. No clinical or demographic factor remained associated with p-tau217 after accounting for the number of analyses performed. Conclusions These findings provide no evidence of a group-level Alzheimer-related p-tau217 elevation in young people with DSRD and support DSRD as a condition distinct from Alzheimer’s disease. However, a single blood measurement cannot exclude Alzheimer pathology in an individual. Longitudinal studies using several complementary biomarkers are needed.

Key findings

• Because people with Down syndrome have a high lifetime risk of Alzheimer’s disease, we examined whether DSRD is associated with an Alzheimer-related pattern of tau pathology.
• Results Median p-tau217 concentrations were similar in the DSRD (0.082 pg/mL), DSwR (0.084 pg/mL), and neurodevelopmental control (0.080 pg/mL) groups (overall comparison, p = 0.57).
• Pairwise comparisons and models accounting for demographic and clinical factors also showed no statistically significant group differences.
• Among participants with DSRD, p-tau217 was not associated with treatment status or abnormalities on brain-wave testing, neuroimaging, or cerebrospinal fluid analysis.
• No clinical or demographic factor remained associated with p-tau217 after accounting for the number of analyses performed.

Why it matters

This study found no significant difference in a blood marker of Alzheimer's tau pathology between young adults with Down syndrome regression disorder, those with Down syndrome without regression, and controls. The results suggest that this regression disorder is not associated with an Alzheimer's-like tau pattern.

Study details

• Study designlongitudinal study
• Participants132
• Evidence strengthModerate

Read the original

• DOI: 10.1038/s43856-026-01921-y
• PubMed: 42897209
• Original source →
• Free full text: Communications Medicine →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{santoro2026-10090373,
  author  = {Santoro, Jonathan Douglas and Abdel‐Latif, Sara and Banerjee, Abhik K. and Mager, Hannah and Silverman, Mackenzie and Kazerooni, Lilia and Otey, Samuel T. and Yousuf, Mariam M and others},
  title   = {{Phosphorylated tau 217 in young adults with Down syndrome and Down syndrome regression disorder}},
  journal = {Communications Medicine},
  year    = {2026},
  doi     = {10.1038/s43856-026-01921-y},
  pmid    = {42897209},
  url     = {https://doi.org/10.1038/s43856-026-01921-y}
}

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