Down syndrome and Alzheimer's disease: Common pathways, common goals

Dean Hartley; Thomas Blumenthal; Maria Carrillo; Gilbert DiPaolo; Lucille Esralew; Katheleen Gardiner; Ann-Charlotte Granholm; Khalid Iqbal; Michael Krams; Cynthia Lemere; Ira Lott; William Mobley; Seth Ness; Ralph Nixon; Huntington Potter; Roger Reeves; Marwan Sabbagh; Wayne Silverman; Benjamin Tycko; Michelle Whitten; Thomas Wisniewski

doi:10.1016/j.jalz.2014.10.007

Down syndrome and Alzheimer's disease: Common pathways, common goals

Alzheimers Dement. 2015 Jun;11(6):700-9. doi: 10.1016/j.jalz.2014.10.007. Epub 2014 Dec 12.

Authors

Dean Hartley¹, Thomas Blumenthal², Maria Carrillo³, Gilbert DiPaolo⁴, Lucille Esralew⁵, Katheleen Gardiner⁶, Ann-Charlotte Granholm⁷, Khalid Iqbal⁸, Michael Krams⁹, Cynthia Lemere¹⁰, Ira Lott¹¹, William Mobley¹², Seth Ness⁹, Ralph Nixon¹³, Huntington Potter¹⁴, Roger Reeves¹⁵, Marwan Sabbagh¹⁶, Wayne Silverman¹⁷, Benjamin Tycko⁴, Michelle Whitten¹⁸, Thomas Wisniewski¹⁹

Affiliations

¹ Medical and Scientific Relations, Alzheimer's Association, Chicago, IL, USA. Electronic address: dhartley@alz.org.
² Linda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA.
³ Medical and Scientific Relations, Alzheimer's Association, Chicago, IL, USA.
⁴ Department of Pathology and Cell Biology, Columbia University Medical Center and The Taub Institute for Research on Alzheimer's Disease and The Aging Brain, New York, NY, USA.
⁵ Department of Behavioral Health, Trinitas Regional Medical Center, Elizabeth, NJ, USA.
⁶ Linda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, USA; Department of Pediatrics, University of Colorado, Denver, CO, USA.
⁷ Department of Neuroscience and the Center on Aging, Medical University of South Carolina, Columbia, SC, USA.
⁸ Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, New York, NY, USA.
⁹ Janssen Research & Development, Raritan, NJ, USA.
¹⁰ Department of Neurology and the Anne Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Pediatrics, University of California, Irvine, CA, USA.
¹² Department of Neurosciences, University of California, San Diego, CA, USA.
¹³ Department of Psychiatry and Cell Biology, New York University, Langone Medical Center, New York, NY, USA.
¹⁴ Linda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, USA; Department of Neurology, University of Colorado, Denver, CO, USA.
¹⁵ Department of Physiology, McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁶ Banner Sun Health Research Institute, Banner Health, Sun City, AZ, USA.
¹⁷ Department of Behavioral Psychology, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁸ Global Down Syndrome Foundation, Denver, CO, USA.
¹⁹ Department of Neurology, Pathology, and Psychiatry, New York University, Langone Medical Center, New York, NY, USA.

Abstract

In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments.

Keywords: ADNI; Alzheimer's disease; Amyloid precursor protein; Animal models; Beta-amyloid; Biomarkers; Clinical trials; Cognitive assessment; DS-Connect; Dementia; Down syndrome; Drug discovery; Neuroimaging; Neuroinflammation; Tau; Trisomy 21; Ts65Dn; Workshop.

MeSH terms

Alzheimer Disease / diagnosis
Alzheimer Disease / drug therapy
Alzheimer Disease / pathology
Alzheimer Disease / physiopathology*
Animals
Clinical Trials as Topic
Congresses as Topic
Disease Models, Animal
Down Syndrome / diagnosis
Down Syndrome / drug therapy
Down Syndrome / pathology
Down Syndrome / physiopathology*
Drug Discovery
Humans
Neuropsychological Tests

Abstract

MeSH terms

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