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

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.

PMID: 25510383
PMCID: PMC4817997
DOI: 10.1016/j.jalz.2014.10.007

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

Dean Hartley et al. Alzheimers Dement. 2015 Jun.

. 2015 Jun;11(6):700-9.

doi: 10.1016/j.jalz.2014.10.007. Epub 2014 Dec 12.

Authors

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.

PMID: 25510383
PMCID: PMC4817997
DOI: 10.1016/j.jalz.2014.10.007

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.

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Figures

**Fig. 1**
Mouse models of Down syndrome (DS). The diagram shows a representation of human chromosome 21, HSA21, and separate mouse chromosomes (10, 16, and 17) that are orthologous to HSA21that have been used to develop mouse models of DS [59,60]. The mouse models diagrammed here represent the triplication of different regions of the various murine chromosomes, except the Tc1 mouse model, that carries a transchromosome with the human HAS21 genes (black boxes are two internal deletions). The most commonly used model is the Ts65DN which represents the triplication of the mouse chromosome (MMU) 16 [79]. Ts1Cje, Ts1Yu and Ts1Rhr are segmental duplications or translocations of different lengths of MMU16 [60].

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical