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

Journal of Clinical Medicine

Brian Chicoine¹  Amy Talboy²  TracieC. Rosser³  H.Diana Rosas⁴  Florence Lai⁴  Carolyn Revta⁵  HowardH. Feldman⁵  Kim Schafer⁵  Ronelyn Chavez⁵  Jennifer Mason⁵  DuviaLara Ledesma⁵  William Mobley⁶  Elizabeth Head⁷  Ira Lott⁸  Eric Doran⁸  Jason Woodward⁹  Anna Esbensen⁹  MargaretB. Pulsifer^1,10  CaseyL. Evans^1,10  AlbertoC. S. Costa^1,11  GeorgeT. Capone^1,12  Kavita Krell^1,13  BrianG. Skotko^1,13  Amy Torres^1,13  Kelsey Haugen^1,13  Stephanie Santoro^1,13  Sarah Hart^1,14  PriyaS. Kishnani^1,14  JeffreyL. Dage^1,15  NicholasKyle Proctor^1,15  DavidC. Airey^1,15  JenniferA. Zimmer^1,15  Angela Britton^1,16  Hampus Hillerstrom^1,16  JamesA. Hendrix^1,16  KelleyM. Faber^1,17  TatianaM. Foroud^1,17  Kristi Wilmes^1,17  Suzanne Hendrix^1,18  Jessie Nicodemus-Johnson^1,18  Cesar Ochoa-Lubinoff^1,19  Jacqueline Chen^1,19  Frederick Schmitt^2,20  AnnaD. Burke^2,21  MelissaR. Stasko^2,22  Thomas Scheidemantel^2,22 

[1] Adult Down Syndrome Center, Advocate Medical Group, 1610 Luther Lane, Park Ridge, IL 60068, USA;Department of Human Genetics, Emory University School of Medicine, 1365 Clifton Road, NE, Building A, Suite 2200, Atlanta, GA 30322, USA;Department of Human Genetics, Emory University, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA;Department of Neurology, Massachusetts General Hospital, McLean Hospital, and Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA;Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA;Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0662, USA;Department of Pathology and Laboratory Medicine, The University of California, Irvine, School of Medicine, 1111 Gillepsie Neuroscience Research Facility, Irvine, CA 92697, USA;Department of Pediatrics, The University of California, Irvine, 333 The City Blvd. West, Suite 800, Orange, CA 92868-4482, USA;Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA;Department of Psychiatry, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA;Division of Neurology and Epilepsy, Department of Pediatrics, Department of Psychiatry, Case Western Reserve University School of Medicine, 10524 Euclid Ave, Cleveland, OH 44106, USA;Down Syndrome Clinic & Research Center, Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA;Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA;Duke University Medical Center, Department of Pediatrics, 2301 Erwin Road, Durham, NC 27705, USA;Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA;LuMind IDSC, 20 Mall Road, Suite 200, Burlington, MA 01803-4126, USA;National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), Indiana University School of Medicine, 410 W 10th St, Indianapolis, IN 46202, USA;Pentara Corporation, 2261 East 3300 South, Suite 200, Millcreek, UT 84109, USA;Rush University Medical Center, Division of Developmental Behavioral Pediatrics, Department of Pediatrics, 1653 W. Congress Pkwy, Chicago, IL 60612, USA;Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St., Lexington, KY 40536, USA;St. Joseph’s Hospital and Medical Center, Department of Neurology, Barrow Neurological Institute, 350 W. Thomas Rd., Phoenix, AZ 85013, USA;University Hospitals Cleveland Medical Center, Department of Psychiatry, Case Western Reserve University School of Medicine, 10524 Euclid Ave, Cleveland, OH 44106, USA;

关键词: Down syndrome;    Alzheimer’s disease;    blood biomarkers;    phosphorylated tau protein;    amyloid β peptide;    neurofilament light chain;   

DOI  :  10.3390/jcm10091907

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown