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The Association between Physical Activity and CAMDEX-DS Changes Prior to the Onset of Alzheimer’s Disease in Down Syndrome
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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

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LuMind IDSC, 20 Mall Road, Suite 200, Burlington, MA 01803-4126, USA
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Eli Lilly and Company, 893 Delaware St. Indianapolis, IN 46225, USA
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St. Joseph’s Hospital and Medical Center, Department of Neurology, Barrow Neurological Institute, 350 W. Thomas Rd., Phoenix, AZ 85013, USA
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Down Syndrome Clinic & Research Center, Kennedy Krieger Institute, 707 N. Broadway, Baltimore, MD 21205, USA
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Department of Neurosciences, Alzheimer’s Disease Cooperative Study, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0949, USA
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Rush University Medical Center, Division of Developmental Behavioral Pediatrics, Department of Pediatrics, 1653 W. Congress Pkwy, Chicago, IL 60612, USA
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Adult Down Syndrome Center, Advocate Medical Group, 1610 Luther Lane, Park Ridge, IL 60068, USA
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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
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Department of Pediatrics, The University of California, Irvine, 333 The City Blvd. West, Suite 800, Orange, CA 92868-4482, USA
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Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
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Division of Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA
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Department of Psychiatry, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
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National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), Indiana University School of Medicine, 410 W 10th St, Indianapolis, IN 46202, USA
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Duke University Medical Center, Department of Pediatrics, 2301 Erwin Road, Durham, NC 27705, USA
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Down Syndrome Program, Division of Medical Genetics and Metabolism, Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA
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Department of Pathology and Laboratory Medicine, The University of California, Irvine, School of Medicine, 1111 Gillepsie Neuroscience Research Facility, Irvine, CA 92697, USA
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Pentara Corporation, 2261 East 3300 South, Suite 200, Millcreek, UT 84109, USA
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Department of Neurology, Massachusetts General Hospital, McLean Hospital, and Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
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Department of Human Genetics, Emory University, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA
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Department of Pediatrics, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA
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University Hospitals Cleveland Medical Center, Department of Psychiatry, Case Western Reserve University School of Medicine, 10524 Euclid Ave, Cleveland, OH 44106, USA
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Sanders-Brown Center on Aging, University of Kentucky, 800 S. Limestone St., Lexington, KY 40536, USA
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Department of Human Genetics, Emory University School of Medicine, 1365 Clifton Road, NE, Building A, Suite 2200, Atlanta, GA 30322, USA
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Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0662, USA
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Author to whom correspondence should be addressed.
Academic Editors: Ann-Charlotte Granholm and Lindsay A. Farrer
J. Clin. Med. 2021, 10(9), 1907; https://doi.org/10.3390/jcm10091907
Received: 27 March 2021 / Revised: 22 April 2021 / Accepted: 27 April 2021 / Published: 28 April 2021
(This article belongs to the Special Issue Aging in Down Syndrome: Latest Clinical Advances and Prospects)
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. View Full-Text
Keywords: Down syndrome; Alzheimer’s disease; blood biomarkers; phosphorylated tau protein; amyloid β peptide; neurofilament light chain; glial fibrillary acidic protein Down syndrome; Alzheimer’s disease; blood biomarkers; phosphorylated tau protein; amyloid β peptide; neurofilament light chain; glial fibrillary acidic protein
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MDPI and ACS Style

Hendrix, J.A.; Airey, D.C.; Britton, A.; Burke, A.D.; Capone, G.T.; Chavez, R.; Chen, J.; Chicoine, B.; Costa, A.C.S.; Dage, J.L.; Doran, E.; Esbensen, A.; Evans, C.L.; Faber, K.M.; Foroud, T.M.; Hart, S.; Haugen, K.; Head, E.; Hendrix, S.; Hillerstrom, H.; Kishnani, P.S.; Krell, K.; Ledesma, D.L.; Lai, F.; Lott, I.; Ochoa-Lubinoff, C.; Mason, J.; Nicodemus-Johnson, J.; Proctor, N.K.; Pulsifer, M.B.; Revta, C.; Rosas, H.D.; Rosser, T.C.; Santoro, S.; Schafer, K.; Scheidemantel, T.; Schmitt, F.; Skotko, B.G.; Stasko, M.R.; Talboy, A.; Torres, A.; Wilmes, K.; Woodward, J.; Zimmer, J.A.; Feldman, H.H.; Mobley, W. 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. J. Clin. Med. 2021, 10, 1907. https://doi.org/10.3390/jcm10091907

AMA Style

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, Mobley W. 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. 2021; 10(9):1907. https://doi.org/10.3390/jcm10091907

Chicago/Turabian Style

Hendrix, James A.; Airey, David C.; Britton, Angela; Burke, Anna D.; Capone, George T.; Chavez, Ronelyn; Chen, Jacqueline; Chicoine, Brian; Costa, Alberto C.S.; Dage, Jeffrey L.; Doran, Eric; Esbensen, Anna; Evans, Casey L.; Faber, Kelley M.; Foroud, Tatiana M.; Hart, Sarah; Haugen, Kelsey; Head, Elizabeth; Hendrix, Suzanne; Hillerstrom, Hampus; Kishnani, Priya S.; Krell, Kavita; Ledesma, Duvia L.; Lai, Florence; Lott, Ira; Ochoa-Lubinoff, Cesar; Mason, Jennifer; Nicodemus-Johnson, Jessie; Proctor, Nicholas K.; Pulsifer, Margaret B.; Revta, Carolyn; Rosas, H. D.; Rosser, Tracie C.; Santoro, Stephanie; Schafer, Kim; Scheidemantel, Thomas; Schmitt, Frederick; Skotko, Brian G.; Stasko, Melissa R.; Talboy, Amy; Torres, Amy; Wilmes, Kristi; Woodward, Jason; Zimmer, Jennifer A.; Feldman, Howard H.; Mobley, William. 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" J. Clin. Med. 10, no. 9: 1907. https://doi.org/10.3390/jcm10091907

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