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

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 tar...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2020-10, Vol.370 (6512), p.61-66
Main Authors: Sierksma, Annerieke, Escott-Price, Valentina, De Strooper, Bart
Format: Article
Language:English
Subjects:
Alzheimer Disease - drug therapy
Alzheimer Disease - genetics
Alzheimer Disease - prevention & control
Animals
Disease Models, Animal
Drug Development
Genetic Predisposition to Disease
Genetic Variation
Humans
Mice
Mice, Transgenic
Molecular Targeted Therapy
Risk
Translational Research, Biomedical
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abb8575