Phosphorylated tau 217 in young adults with Down syndrome and Down syndrome regression disorder.
6 affiliations
- 1Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA. [email protected].
- 2Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. [email protected].
- 3Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
- 4Division of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA, USA.
- 5National Institutes of Health, Bethesda, MD, USA.
- 6Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
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.
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BibTeX
@article{santoro2026phosphorylated,
title = {{Phosphorylated tau 217 in young adults with Down syndrome and Down syndrome regression disorder.}},
author = {Jonathan D Santoro and Sara Abdel-Latif and Abhik K Banerjee and Hannah Mager and Mackenzie Silverman and Lilia Kazerooni and Samuel T Otey and Mariam M Yousuf and Maeve C Lucas and Zinayida Schlachetzki and Robert A Rissman and Michael S Rafii},
journal = {Communications medicine},
year = {2026},
month = sep,
doi = {10.1038/s43856-026-01921-y},
url = {https://europepmc.org/article/MED/42897209},
note = {CC BY},
}
RIS
TY - JOUR
TI - Phosphorylated tau 217 in young adults with Down syndrome and Down syndrome regression disorder.
AU - Jonathan D Santoro
AU - Sara Abdel-Latif
AU - Abhik K Banerjee
AU - Hannah Mager
AU - Mackenzie Silverman
AU - Lilia Kazerooni
AU - Samuel T Otey
AU - Mariam M Yousuf
AU - Maeve C Lucas
AU - Zinayida Schlachetzki
AU - Robert A Rissman
AU - Michael S Rafii
PY - 2026
DA - 2026/09/01
JO - Communications medicine
DO - 10.1038/s43856-026-01921-y
UR - https://europepmc.org/article/MED/42897209
AB - 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.
SN - 2730-664X
ER -