Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

• Type of Material: Article
• Authors: Amy Talboy, Emory University; James A Hendrix, LuMind IDSC; David C Airey, Eli Lilly & Company; Angela Britton, LuMind IDSC; Anna D Burke, St Josephs Hospital; George T Capone, Kennedy Krieger Institute; Ronelyn Chavez, University of California San Diego; Jacqueline Chen, Rush University; Brian Chicoine, Advocate Medical Group; Alberto CS Costa, Case Western Reserve University; Jeffrey L Dage, Eli Lilly & Company; Eric Doran, University of California Irvine; Anna Esbensen, University of Cincinnati; Casey L Evans, Massachusetts General Hospital; Kelley M Faber, Indiana University School of Medicine; Tatiana M Foroud, Indiana University School of Medicine; Sarah Hart, Duke University; Kelsey Haugen, Massachusetts General Hospital; Elizabeth Head, University of California Irvine; Suzanne Hendrix, Pentara Corporation; Hampus Hillerstrom, LuMind IDSC; Priya S Kishnani, Duke University; Kavita Krell, Massachusetts General Hospital; Duvia Lara Ledesma, University of California San Diego; Florence Lai, Massachusetts General Hospital; Ira Lott, University of California Irvine; Cesar Ochoa-Lubinoff, Rush University; Jennifer Mason, University of California San Diego; Jessie Nicodemus-Johnson, Pentara Corporation; Nicholas Kyle Proctor, Eli Lilly and Company; Margaret B Pulsifer, Massachusetts General Hospital; Carolyn Revta, University of California San Diego; Diana H Rosas, Massachusetts General Hospital; Jennifer Rosser, Emory University; Stephanie Santoro, Massachusetts General Hospital; Kim Schafer, University of California San Diego; Thomas Scheidemantel, Case Western Reserve University; Frederick Schmitt, University of Kentucky; Brian G Skotko, Massachusetts General Hospital; Melissa R Stasko, Case Western Reserve University; Amy Torres, Massachusetts General Hospital; Kristi Wilmes, Indiana Univ Sch Med; Jason Woodward, University of Cincinnati; Jennifer A Zimmer, Eli Lilly and Company; Howard H Feldman, University of California San Diego; William Mobley, University of California San Diego
• Language: English
• Date: 2021-05-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/jcm10091907
• Title of Journal or Parent Work: JOURNAL OF CLINICAL MEDICINE
• Volume: 10
• Issue: 9
• Grant/Funding Information: The LIFE-DSR study is funded by the LuMind IDSC Foundation. Eli Lilly provided the analysis of the plasma biomarkers to LuMind IDSC as an in-kind contribution. Samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible.
• Keywords: neurofilament light chain; Down syndrome; ADULTS; blood biomarkers; Medicine, General & Internal; Science & Technology; s disease; phosphorylated tau protein; Life Sciences & Biomedicine; glial fibrillary acidic protein; DEMENTIA; General & Internal Medicine; amyloid β Alzheimer’ peptide
• Research Categories: Health Sciences, Medicine and Surgery

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 (Aβ1-40, Aβ1-42), 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 Examina-tion (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 ap-proximately 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.