Translating genetic risk of Alzheimer’s disease into mechanistic insight and drug targets

Author:

Sierksma Annerieke12ORCID,Escott-Price Valentina34ORCID,De Strooper Bart125ORCID

Affiliation:

1. VIB Center for Brain & Disease Research, Leuven, Belgium.

2. Laboratory for the Research of Neurodegenerative Diseases, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), Leuven, Belgium.

3. Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

4. UK Dementia Research Institute, Cardiff University, Cardiff, UK.

5. UK Dementia Research Institute, University College London, London, UK.

Abstract

To provide better prevention and treatment, we need to understand the environmental and genetic risks of Alzheimer’s disease (AD). However, the definition of AD has been confounded with dementia in many studies. Thus, overinterpretation of genetic findings with regard to mechanisms and drug targets may explain, in part, controversies in the field. Here, we analyze the different forms of genetic risk of AD and how these can be used to model disease. We stress the importance of studying gene variants in the right cell types and in the right pathological context. The lack of mechanistic understanding of genetic variation has become the major bottleneck in the search for new drug targets for AD.

Funder

Alzheimer's Association

H2020 European Research Council

EU Joint Programme – Neurodegenerative Disease Research

KU Leuven

Vlaams Instituut voor Biotechnologie

Internationale Stichting Alzheimer Onderzoek

UK Dementia Research Institute

Leuven Universitair Fonds

Welsh Government

MRC Centre for Neuropsychiatric Genetics and Genomics

Fonds voor Wetenschappelijk Onderzoek

Geneeskundige Stichting Koningin Elisabeth

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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