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Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine
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Alzheimer's disease (AD) is the leading cause of dementia in the United States and afflicts >5.7 million Americans in 2018. Therapeutic options remain extremely limited to those that are symptom targeting, while no drugs have been approved for the modification or reversal of the disease itself. Risk factors for AD including aging, the female sex, as well as carrying an APOE4 genotype. These risk factors have been extensively examined in the literature, while less attention has been paid to modifiable risk factors, including lifestyle, and environmental risk factors such as exposures to air pollution and pesticides. This review highlights the most recent data on risk factors in AD and identifies gene by environment interactions that have been investigated. It also provides a suggested framework for a personalized therapeutic approach to AD, by combining genetic, environmental and lifestyle risk factors. Understanding modifiable risk factors and their interaction with non-modifiable factors (age, susceptibility alleles, and sex) is paramount for designing personalized therapeutic interventions.
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“an individual’s genetic background has been reported to influence how they respond to environmental exposures or lifestyle factors [269]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [269]
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“Several modifiable risk factors have been associated with AD risk across populations, including educational attainment, obesity, cholesterol levels, social isolation, alcohol consumption, and exposure to pesticides [269, 270]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [269]
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Metadata
- Authors
- Eid, A., Mhatre, I., & Richardson, J. R.
- Affiliations
- Florida International University (US)
- Corresponding author
- Richardson, Jason R.
- ORCID
- Richardson, Jason R.
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 199
- Pages
- 173-187
- ISSN
- 0163-7258 (ISSN-L)
- PMC
- PMC6827882
- OpenAlex
- W2922392851
- Cited by
- 164
- References
- 268
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 34 · 2023: 20 · 2022: 15 · 2021: 13 · 2020: 24 · 2019: 9
- FWCI
- 1.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01ES021800, R01ES026057, R01ES026067-S2, U01NS108956)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- Alzheimer's disease, gene-environment interaction, modifiable risk factors, lifestyle risk factors, air pollution exposure, pesticide exposure, APOE ε4, sex differences, aging, personalized medicine, precision medicine, dementia
- MeSH terms
- Alzheimer Disease, Animals, Humans, Risk Factors, Precision Medicine, Gene-Environment Interaction
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