Journal of Clinical Medicine (Apr 2021)
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
- James A. Hendrix,
- David C. Airey,
- Angela Britton,
- Anna D. Burke,
- George T. Capone,
- Ronelyn Chavez,
- Jacqueline Chen,
- Brian Chicoine,
- Alberto C. S. Costa,
- Jeffrey L. Dage,
- Eric Doran,
- Anna Esbensen,
- Casey L. Evans,
- Kelley M. Faber,
- Tatiana M. Foroud,
- Sarah Hart,
- Kelsey Haugen,
- Elizabeth Head,
- Suzanne Hendrix,
- Hampus Hillerstrom,
- Priya S. Kishnani,
- Kavita Krell,
- Duvia Lara Ledesma,
- Florence Lai,
- Ira Lott,
- Cesar Ochoa-Lubinoff,
- Jennifer Mason,
- Jessie Nicodemus-Johnson,
- Nicholas Kyle Proctor,
- Margaret B. Pulsifer,
- Carolyn Revta,
- H. Diana Rosas,
- Tracie C. Rosser,
- Stephanie Santoro,
- Kim Schafer,
- Thomas Scheidemantel,
- Frederick Schmitt,
- Brian G. Skotko,
- Melissa R. Stasko,
- Amy Talboy,
- Amy Torres,
- Kristi Wilmes,
- Jason Woodward,
- Jennifer A. Zimmer,
- Howard H. Feldman,
- William Mobley
Affiliations
- James A. Hendrix
- LuMind IDSC, 20 Mall Road, Suite 200, Burlington, MA 01803-4126, USA
- David C. Airey
- Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA
- Angela Britton
- LuMind IDSC, 20 Mall Road, Suite 200, Burlington, MA 01803-4126, USA
- Anna D. Burke
- St. Joseph’s Hospital and Medical Center, Department of Neurology, Barrow Neurological Institute, 350 W. Thomas Rd., Phoenix, AZ 85013, USA
- George T. Capone
- Down Syndrome Clinic & Research Center, Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA
- Ronelyn Chavez
- Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
- Jacqueline Chen
- Rush University Medical Center, Division of Developmental Behavioral Pediatrics, Department of Pediatrics, 1653 W. Congress Pkwy, Chicago, IL 60612, USA
- Brian Chicoine
- Adult Down Syndrome Center, Advocate Medical Group, 1610 Luther Lane, Park Ridge, IL 60068, USA
- Alberto C. S. Costa
- 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
- Jeffrey L. Dage
- Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA
- Eric Doran
- Department of Pediatrics, The University of California, Irvine, 333 The City Blvd. West, Suite 800, Orange, CA 92868-4482, USA
- Anna Esbensen
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
- Casey L. Evans
- Department of Psychiatry, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Kelley M. Faber
- National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), Indiana University School of Medicine, 410 W 10th St, Indianapolis, IN 46202, USA
- Tatiana M. Foroud
- National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), Indiana University School of Medicine, 410 W 10th St, Indianapolis, IN 46202, USA
- Sarah Hart
- Duke University Medical Center, Department of Pediatrics, 2301 Erwin Road, Durham, NC 27705, USA
- Kelsey Haugen
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Elizabeth Head
- Department of Pathology and Laboratory Medicine, The University of California, Irvine, School of Medicine, 1111 Gillepsie Neuroscience Research Facility, Irvine, CA 92697, USA
- Suzanne Hendrix
- Pentara Corporation, 2261 East 3300 South, Suite 200, Millcreek, UT 84109, USA
- Hampus Hillerstrom
- LuMind IDSC, 20 Mall Road, Suite 200, Burlington, MA 01803-4126, USA
- Priya S. Kishnani
- Duke University Medical Center, Department of Pediatrics, 2301 Erwin Road, Durham, NC 27705, USA
- Kavita Krell
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Duvia Lara Ledesma
- Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
- Florence Lai
- Department of Neurology, Massachusetts General Hospital, McLean Hospital, and Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
- Ira Lott
- Department of Pediatrics, The University of California, Irvine, 333 The City Blvd. West, Suite 800, Orange, CA 92868-4482, USA
- Cesar Ochoa-Lubinoff
- Rush University Medical Center, Division of Developmental Behavioral Pediatrics, Department of Pediatrics, 1653 W. Congress Pkwy, Chicago, IL 60612, USA
- Jennifer Mason
- Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
- Jessie Nicodemus-Johnson
- Pentara Corporation, 2261 East 3300 South, Suite 200, Millcreek, UT 84109, USA
- Nicholas Kyle Proctor
- Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA
- Margaret B. Pulsifer
- Department of Psychiatry, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Carolyn Revta
- Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
- H. Diana Rosas
- Department of Neurology, Massachusetts General Hospital, McLean Hospital, and Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
- Tracie C. Rosser
- Department of Human Genetics, Emory University, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA
- Stephanie Santoro
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Kim Schafer
- Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
- Thomas Scheidemantel
- University Hospitals Cleveland Medical Center, Department of Psychiatry, Case Western Reserve University School of Medicine, 10524 Euclid Ave, Cleveland, OH 44106, USA
- Frederick Schmitt
- Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St., Lexington, KY 40536, USA
- Brian G. Skotko
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Melissa R. Stasko
- University Hospitals Cleveland Medical Center, Department of Psychiatry, Case Western Reserve University School of Medicine, 10524 Euclid Ave, Cleveland, OH 44106, USA
- Amy Talboy
- Department of Human Genetics, Emory University School of Medicine, 1365 Clifton Road, NE, Building A, Suite 2200, Atlanta, GA 30322, USA
- Amy Torres
- Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
- Kristi Wilmes
- National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), Indiana University School of Medicine, 410 W 10th St, Indianapolis, IN 46202, USA
- Jason Woodward
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
- Jennifer A. Zimmer
- Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA
- Howard H. Feldman
- Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
- William Mobley
- Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0662, USA
- DOI
- https://doi.org/10.3390/jcm10091907
- Journal volume & issue
-
Vol. 10,
no. 9
p. 1907
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 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.
Keywords
- Down syndrome
- Alzheimer’s disease
- blood biomarkers
- phosphorylated tau protein
- amyloid β peptide
- neurofilament light chain