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

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

Forensic & Neurodevelopmental Sciences

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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.

Original language	English
Pages (from-to)	703-713
Journal	Alzheimers & Dementia
Volume	4
Early online date	13 Dec 2018
DOIs	https://doi.org/10.1016/j.trci.2018.10.006
Publication status	E-pub ahead of print - 13 Dec 2018

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title = "Alzheimer's disease in Down syndrome: An overlooked population for prevention trials",

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.",

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T2 - An overlooked population for prevention trials

AU - Strydom, André

AU - Coppus, Antonia

AU - Blesa, Rafael

AU - Danek, Adrian

AU - Fortea, Juan

AU - Hardy, John

AU - Levin, Johannes

AU - Nuebling, Georg

AU - Rebillat, Anne-sophie

AU - Ritchie, Craig

AU - Van Duijn, Cornelia

AU - Zaman, Shahid

AU - Zetterberg, Henrik

PY - 2018/12/13

Y1 - 2018/12/13

N2 - 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.

AB - 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.

U2 - 10.1016/j.trci.2018.10.006

DO - 10.1016/j.trci.2018.10.006

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JO - Alzheimers & Dementia

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

Abstract

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