Translating genetic risk of Alzheimer's disease into mechanistic insight and drug targets
- PMID: 33004512
- DOI: 10.1126/science.abb8575
Translating genetic risk of Alzheimer's disease into mechanistic insight and drug targets
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.
Copyright © 2020, American Association for the Advancement of Science.
Similar articles
-
Research on Alzheimer's Disease (AD) Involving the Use of In vivo and In vitro Models and Mechanisms.Cent Nerv Syst Agents Med Chem. 2025;25(2):123-142. doi: 10.2174/0118715249293642240522054929. Cent Nerv Syst Agents Med Chem. 2025. PMID: 38803173 Review.
-
"Amyloid-beta accumulation cycle" as a prevention and/or therapy target for Alzheimer's disease.Aging Cell. 2020 Mar;19(3):e13109. doi: 10.1111/acel.13109. Epub 2020 Jan 25. Aging Cell. 2020. PMID: 31981470 Free PMC article. Review.
-
Using mouse models to understand Alzheimer's disease mechanisms in the context of trisomy of chromosome 21.Prog Brain Res. 2020;251:181-208. doi: 10.1016/bs.pbr.2019.10.004. Epub 2019 Nov 29. Prog Brain Res. 2020. PMID: 32057307 Review.
-
The Alzheimer's disease drug development landscape.Alzheimers Res Ther. 2021 Nov 11;13(1):186. doi: 10.1186/s13195-021-00927-z. Alzheimers Res Ther. 2021. PMID: 34763720 Free PMC article.
-
Epigenetic regulation in Alzheimer's disease: is it a potential therapeutic target?Expert Opin Ther Targets. 2021 Apr;25(4):283-298. doi: 10.1080/14728222.2021.1916469. Epub 2021 May 13. Expert Opin Ther Targets. 2021. PMID: 33843425 Review.
Cited by
-
Biomarkers for neurodegenerative diseases.Nat Med. 2021 Jun;27(6):954-963. doi: 10.1038/s41591-021-01382-x. Epub 2021 Jun 3. Nat Med. 2021. PMID: 34083813 Review.
-
Machine learning for the life-time risk prediction of Alzheimer's disease: a systematic review.Brain Commun. 2021 Oct 21;3(4):fcab246. doi: 10.1093/braincomms/fcab246. eCollection 2021. Brain Commun. 2021. PMID: 34805994 Free PMC article. Review.
-
Functional near-infrared spectroscopy and vagus somatosensory evoked potentials add to the power of established parameters such as poor cognitive performance, dsyosmia and APOe genotype to predict cognitive decline over 8 years in the elderly.J Neural Transm (Vienna). 2025 Mar;132(3):455-468. doi: 10.1007/s00702-024-02859-y. Epub 2024 Nov 13. J Neural Transm (Vienna). 2025. PMID: 39535568 Free PMC article.
-
A Novel Missense Variant in SORBS2 Is Causative With Familial Alzheimer's Disease.CNS Neurosci Ther. 2025 Feb;31(2):e70256. doi: 10.1111/cns.70256. CNS Neurosci Ther. 2025. PMID: 39912518 Free PMC article.
-
MDGA1 negatively regulates amyloid precursor protein-mediated synapse inhibition in the hippocampus.Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2115326119. doi: 10.1073/pnas.2115326119. Proc Natl Acad Sci U S A. 2022. PMID: 35074912 Free PMC article.
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Medical