487 - Tau protein in children with Down syndrome: Role in early-onset Alzheimer's Disease and neonatal physiology

Publication Number: 1467.487

Robert McCarthy, Trinity College Dublin/Children's Health Ireland, Dublin, Dublin, Ireland; Lynne A. Kelly, Trinity Translational Medicine Institute, Faculty of Health Sciences, Trinity College Dublin, Dublin, Dublin, Ireland; Joanne Balfe, Children's Health Ireland, Dublin, Dublin, Ireland; Beth Corcoran, Trinity College Dublin, Dublin 14, Dublin, Ireland; Eleanor J. Molloy, Trinity College Dublin, Dublin, Dublin, Ireland; Fiona Mc Grane, Children's Health Ireland, Dublin, Dublin, Ireland

Background: Early onset dementia is a well-recognised complication in adults with Down’s Syndrome (DS). While post-mortem analysis of brain tissue has revealed pathological levels of amyloid plaques and neurofibrillary tangles in patients as young as 40, specific biomarkers to predict the onset of dementia in DS remains largely unknown. One such marker which has been hypothesized as a possible means of early detection is the Tau protein, which plays a significant role in stabilizing neuronal structure and facilitating transport within these cells. Multiple studies have demonstrated elevated levels of this protein among the adult DS population, but not in young children.

Objective: The goal of this study was to analyse the levels of total Tau protein in blood samples of children with Down Syndrome and compare them to age-matched controls.

Design/Methods: Blood samples were taken from children with Down’s Syndrome and age-matched controls. Total Tau was evaluated using the MSD®MULTI-SPOT assay system, with U-PLEX platforms calibration curves showing the expected signals and precision for this protein

Results: 119 children were included with ages ranged from 3 months to 16 years in children with DS (mean = 5.335), with other demographics including documented prematurity, significant comorbidities, and previous neuroimaging. There were significantly lower levels of total Tau protein in the serum of children with DS compared to controls, with a mean of 2.24pg/ml (95% CI 1.56 – 2.92pg/ml, SD 2.68pg/ml p < 0.0001) in the DS compared to 13,521pg/ml (95% CI 1,168 – 25874pg/ml, SD 48,405pg/ml, p < 0.0001) in controls. Sex, gestational age, or associated co-morbidities did not significantly alter the levels of Tau.

Conclusion(s): Elevations in Tau protein may only begin to occur as DS patients move into adult years, coinciding with the early stages of dementia, thus it could be a useful marker to include in routine monitoring. Total Tau levels in control children were generally higher than those with DS, correlating with other studies that have hypothesized the physiological role Tau protein may play in early life, separate from the pathological processes seen in neurodegenerative conditions in later years. Further research could focus on whether specific isomers of Tau protein could act as biomarkers to help identify and monitor evolving dementia in those with Downs Syndrome.

Total Tau Protein in Control vs Down Syndrome Children
Box and whisker chart for Tau protein.pdf