Alzheimer's disease in Down syndrome: An overlooked population for prevention trials

André Strydom; Antonia Coppus; Rafael Blesa; Adrian Danek; Juan Fortea; John Hardy; Johannes Levin; Georg Nuebling; Anne-Sophie Rebillat; Craig Ritchie; Cornelia van Duijn; Shahid Zaman; Henrik Zetterberg

doi:10.1016/j.trci.2018.10.006

Alzheimer's disease in Down syndrome: An overlooked population for prevention trials

Alzheimers Dement (N Y). 2018 Dec 13:4:703-713. doi: 10.1016/j.trci.2018.10.006. eCollection 2018.

Authors

André Strydom^{1

2

3

4}, Antonia Coppus^{5

6}, Rafael Blesa^{7

8}, Adrian Danek⁹, Juan Fortea^{7

8

10}, John Hardy^{3

11

12}, Johannes Levin^{9

13}, Georg Nuebling⁹, Anne-Sophie Rebillat¹⁴, Craig Ritchie¹⁵, Cornelia van Duijn¹⁶, Shahid Zaman^{17

18}, Henrik Zetterberg^{11

19

20

21}

Affiliations

¹ Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.
² Division of Psychiatry, University Collee London, London, UK.
³ The London Down Syndrome Consortium (LonDownS), UK.
⁴ South London and Maudsley NHS Foundation Trust, London, UK.
⁵ Dichterbij, Center for Intellectual Disabilities, Gennep, the Netherlands.
⁶ Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands.
⁷ Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau- Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain.
⁸ Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain.
⁹ Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany.
¹⁰ Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain.
¹¹ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
¹² Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.
¹³ German Center for Neurodegenerative Diseases (DZNE) site Munich, Munich, Germany.
¹⁴ Institut Jérôme Lejeune, Paris, France.
¹⁵ Centre for Clinical Brain Sciences, Dementia Prevention Research Group, University of Edinburgh.
¹⁶ Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.
¹⁷ Cambridge Intellectual & Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Cambridge, UK.
¹⁸ Cambridgeshire & Peterborough NHS Foundation Trust (CBFT), Fulbourn Hospital, Cambridge, UK.
¹⁹ UK Dementia Research Institute at UCL, London, UK.
²⁰ Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
²¹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Abstract

The discovery that adults with Down syndrome (DS) have neuropathological features identical to individuals with sporadic Alzheimer's disease (AD) played a key role in the identification of the amyloid precursor protein gene on chromosome 21 and resulted in the amyloid cascade hypothesis. Individuals with DS have a lifetime risk for dementia in excess of 90%, and DS is now acknowledged to be a genetic form of AD similar to rare autosomal-dominant causes. Just as DS put the spotlight on amyloid precursor protein mutations, it is also likely to inform us of the impact of manipulating the amyloid pathway on treatment outcomes in AD. Ironically, however, individuals with DS are usually excluded from AD trials. This review will discuss primary and secondary prevention trials for AD in DS and the potential barriers and solutions to such trials and describe the Europe-wide Horizon21 Consortium to establish a DS-AD prevention clinical trials network.

Keywords: APP; Alzheimer's disease; Amyloid; Biomarkers; Dementia; Down syndrome; Prevention; Randomized controlled trials; Trisomy 21.

Publication types

Review

Abstract

Publication types

Grants and funding