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

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

Strydom A1,2,3,4, Coppus A5,6, Blesa R7,8, Danek A9, Fortea J7,8,10, Hardy J3,11,12, Levin J9,13, Nuebling G9, Rebillat AS14, Ritchie C15, van Duijn C16, Zaman S17,18, Zetterberg H11,19,20,21.

Author information

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

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