Journal of Clinical Medicine | April 28, 2021

Hendrix JA, Airey DC, Britton A, Burke AD, Capone GT, Chavez R, Chen J, Chicoine B, Costa ACS, Dage JL, Doran E, Esbensen A, Evans CL, Faber KM, Foroud TM, Hart S, Haugen K, Head E, Hendrix S, Hillerstrom H, Kishnani PS, Krell K, Ledesma DL, Lai F, Lott I, Ochoa-Lubinoff C, Mason J, Nicodemus-Johnson J, Proctor NK, Pulsifer MB, Revta C, Rosas HD, Rosser TC, Santoro S, Schafer K, Scheidemantel T, Schmitt F, Skotko BG, Stasko MR, Talboy A, Torres A, Wilmes K, Woodward J, Zimmer JA, Feldman HH and Mobley W

J. Clin. Med. 2021, 10(9), 1907

DOI: https://doi.org/10.3390/jcm10091907

Abstract

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ_1-40, Aβ_1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.