The DOI matches its Crossref record; 264 of the 268 references it cites were found in a registry or an index.
Gene-environment interactions in Alzheimer's disease: A potential path to precision medicine
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806
Brunekreef, B., & Holgate, S. T. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11274-8 · Cited by 4,701
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Hearing loss and cognitive decline in older adults
Lin, F. R., Yaffe, K., Xia, J., Xue, Q.-L., Harris, T. B., Purchase-Helzner, E., Satterfield, S., Ayonayon, H. N., Ferrucci, L., Simonsick, E. M., et al. (2013) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2013.1868 · Cited by 4,017
Disease control priorities in developing countries
(2006) · Choice Reviews Online · doi:10.5860/choice.44-0343 · Cited by 3,636
Impact of pesticides use in agriculture: their benefits and hazards
Aktar, M. W., Sengupta, D., & Chowdhury, A. (2009) · Interdisciplinary Toxicology · doi:10.2478/v10102-009-0001-7 · Cited by 3,588
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.263 · Cited by 3,459
Flagged first, then by citations
4 of the 268 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 101–164 of 164
Yaghmaei, E., Pierce, A., Lu, H., Patel, Y. M., Ehwerhemuepha, L., Rezaie, A., Sajjadi, S. A., & Rakovski, C. S. (2023) · PLoS ONE · doi:10.1371/journal.pone.0291362 · Cited by 6
Tsamou, M., Carpi, D., Pistollato, F., & Roggen, E. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-215434 · Cited by 6
Rikos, D., Siokas, V., Mentis, A. A., Aloizou, A., Liampas, I., Tsouris, Z., Peristeri, E., Stamati, P., Hadjigeorgiou, G. M., & Dardiotis, E. (2022) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2150844 · Cited by 15
Understanding the Intricate Role of Exosomes in Pathogenesis of Alzheimer’s Disease
Chauhan, S., Behl, T., Sehgal, A., Singh, S., Sharma, N., Gupta, S., Albratty, M., Najmi, A., Meraya, A. M., & Alhazmi, H. A. (2022) · Neurotoxicity Research · doi:10.1007/s12640-022-00621-4 · Cited by 6
Alghamdi, A., Koen, E., Helmantel, M., Rafie, K., Dolga, A. M., Munster, B. C. V., & Hak, E. (2025) · Pharmaceuticals · doi:10.3390/ph18050722 · Cited by 5
Precision health in Alzheimer disease: Risk assessment‐based strategies
Azar, J., Salama, M., Chidambaram, S. B., Al‐Balushi, B., Essa, M. M., & Qoronfleh, M. W. (2021) · Precision Medical Sciences · doi:10.1002/prm2.12036 · Cited by 7
The impact of APOE ε4 in Alzheimer’s disease: a meta-analysis of voxel-based morphometry studiesPreprint
Bailey, M., Ilchovska, Z. G., Hosseini, A. A., & Jung, J. (2024) · medRxiv · doi:10.1101/2024.05.10.24307165 · Cited by 5
Ghaderi, S., Mohammadi, S., & Fatehi, F. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111444 · Cited by 4
Exploring neuron-specific steroid synthesis and DHEAS therapy in Alzheimer's disease
Lin, H.-Y., Feng, Y., Kao, T., Chen, H.-C., Chen, G.-Y., Ko, C., & Hsu, T. (2024) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2024.106585 · Cited by 4
Examining APOE ε4 and Longitudinal Vascular Brain Injury
Hayes, C. A., Odden, M. C., Levendovszky, S. R., Buchwald, D., Verney, S. P., Shibata, D. K., Zhang, Y., Ali, T., & Suchy‐Dicey, A. M. (2025) · Neurology Open Access · doi:10.1212/wn9.0000000000000059 · Cited by 3
Alameen, A. A. M., Al-Kuraishy, H. M., Abdelaziz, A. M., Al-Gareeb, A. I., Albuhadily, A. K., & Batiha, G. E. (2026) · Life Sciences · doi:10.1016/j.lfs.2026.124578 · Cited by 3
Amiri, S., Jiang, L., Manson, S. M., & Buchwald, D. (2023) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000555 · Cited by 3
Oral Microbiota in Patients with Alzheimer’s Disease: A Systematic Review
Pruntel, S. M., Leusenkamp, L. A., Zaura, E., Vissink, A., & Visser, A. (2024) · Applied Sciences · doi:10.3390/app14198869 · Cited by 3
Leinwand, B., Guorong Wu, A., & Pipiras, V. (2020) · IEEE International Symposium on Biomedical Imaging (ISBI) · doi:10.1109/isbi45749.2020.9098324 · Cited by 3
Hermes, S., Cady, J., Armentrout, S. L., O’Connor, J., Carlson, S. E., Cruchaga, C., Wingo, T. S., Greytak, E. M., & Initiative, T. A. D. N. (2023) · medRxiv · doi:10.1101/2023.02.10.23285766 · Cited by 3
Yakubu, A., Adedeji, I. A., Maduka, O. C., Jegede, A. S., & Adebamowo, C. (2024) · BMC Medical Ethics · doi:10.1186/s12910-024-01141-w · Cited by 3
The role of genetic polymorphisms on drug response in Alzheimer’s disease: a systematic review
Climacosa, F. M. M., Ornos, E. D. B., Gapaz, N. C. L. L., Guantia, M. G. R., Cruz, J. M. C., Manalo, R. V. M., Yu, M. L., Qureshi, A. P., Carampel, A. C., Asis, J. L. B., et al. (2025) · BMC Medical Genomics · doi:10.1186/s12920-025-02225-1 · Cited by 3
Attia, M. S. M., Ahmad, S. F., Nadeem, A., Ansari, M. A., Al‐Hamamah, M. A., Harisa, G. I., Bakheet, S. A., Emran, T. B., Singh, T., & Attia, S. M. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-026-01870-4 · Cited by 3
Migliorati, M., Manrique, C., Rahrah, M., Escoffier, G., Ahmadi, A. E., Girard, S. D., Khrestchatisky, M., Rivera, S., Baranger, K., & Roman, F. S. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220281 · Cited by 2
Epigenetic regulons in Alzheimer's disease
Raval, M., Mishra, S., & Tiwari, A. K. (2023) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2023.01.012 · Cited by 2
Toward the Next Generation of Precision Medicine
Verhulst, B., & Benstock, S. E. (2023) · Policy Insights from the Behavioral and Brain Sciences · doi:10.1177/23727322231197765 · Cited by 2
Trevisan, K., Cristina-Pereira, R., Santos, B. R., Mendonça, P. E., da Silva, H. T., Gonçalves-Mendes, M. T., & Aversi‐Ferreira, T. A. (2024) · International Neuropsychiatric Disease Journal · doi:10.9734/indj/2024/v21i4441 · Cited by 2
Tan, M. S., Cheah, P., Chin, A., Looi, L., & Chang, S. (2024) · PeerJ · doi:10.7717/peerj.17643 · Cited by 2
Pilkay, S. R., Nolasco, M., Nunes, S., Riffer, A., Femia, D., Halevy, D., Veerman, T., Heiland, S., Suwannimit, N., Trexler, N., et al. (2024) · Brain and Behavior · doi:10.1002/brb3.3426 · Cited by 1
John, A., Desai, R., Bartrés‐Faz, D., Cadar, D., Gaysina, D., Gonzalez, A. S., Marchant, N. L., Willroth, E. C., Richards, M., Saunders, R., et al. (2025) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.70120 · Cited by 1
Azmoun, S., Lewis, F. C., Shoieb, D., Jin, Y., Colicino, E., Mhatre‐Winters, I., Gu, H., Krishnamurthy, H. K., Richardson, J. R., Placidi, D., et al. (2025) · Brain Sciences · doi:10.3390/brainsci15080829 · Cited by 1
Self-citationSex differences in APOE- and PICALM-related cognitive profiles in healthy middle-aged adults
Bednorz, A., Trybek, P., Hoang, M. T., & Religa, D. (2026) · Frontiers in Aging · doi:10.3389/fragi.2025.1694701 · Cited by 1
Ran, S., Zhang, J., Cai, M., Chen, L., Qian, Z. M., Tian, F., Wu, G., Boyd, R., McMillin, S. E., Zeng, H.-C., et al. (2026) · GeroScience · doi:10.1007/s11357-026-02102-4 · Cited by 1
Gazcón-Rivas, C. P., Roa-Bruzón, I. Y., Almira, L. F. D., Valdez-Gaxiola, C. A., Dumois‐Petersen, S., Eduardo Figuera, L., Ramos, A. Q., Gurrola‐Díaz, C. M., Ortuño‐Sahagún, D., Valle, Y., et al. (2026) · Medical Sciences · doi:10.3390/medsci14020228 · Cited by 1
Marola, O. J., Uyar, A., Keezer, K. J., Chie, J. A. K. C., Elk, K. J., Cullen, A. E., Eldridge, K., Persohn, S. A., Kanyinda, J. N., Whitesell, J. D., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71476 · Cited by 2
Morsy, N., El‐Shiekh, R. A., Ebrahium, M. M., & Srour, A. M. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110245 · Cited by 1
Late Onset Alzheimer Dementia in Patients with Genotype E3/E4: A Case Report
Laksmidewi, A. A. A. P., & Rau, C. P. V. (2021) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2021.5583 · Cited by 1
Wihadmadyatami, H., & Kusindarta, D. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15717-2.00120-7 · Cited by 1
Li, J., Fu, J., Zheng, Z., Zhu, X., Han, X., & Li, J. (2020) · doi:10.21203/rs.3.rs-25884/v1 · Cited by 1
Can Brain Health Interventions Reduce Mexico’s Dementia Burden? An Essay
Vega, W. A., & Gutiérrez‐Robledo, L. M. (2021) · Springer eBooks · doi:10.1007/978-3-030-70119-2_13
Epigenetic programming of human disease and aging
Rivero-Segura, N. A., Castro-Morales, D., Beristain-Pozos, J. D., Sandoval-Rodríguez, F. E., & Gómez-Verján, J. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-21863-7.00017-2
Chujan, S., Cholpraipimolrat, W., & Satayavivad, J. (2023) · Biochemical Genetics · doi:10.1007/s10528-023-10549-9
Mustaq, M., Ahmed, N., Mahbub, S., Li, C., Miyaoka, Y., Julia, T. C. W., Andrews, S. J., Bayzid, M. S., & Initiative, T. A. D. N. (2023) · medRxiv · doi:10.1101/2023.11.28.23299110
New Genetic Loci Discovery for Alzheimer’s Disease Using Explainable Deep Neural NetworksPreprint
Gkertsou, C., Parameshwarappa, A. K., Shiyanbola, A., Balkhiyarova, Z., Kouchaki, S., Prokopenko, I., Lagou, V., & Demirkan, A. (2023) · Preprints.org · doi:10.1101/2023.12.11.23299839
Insights into the Pathogenesis of Alzheimer’s Disease for Better Therapeutics
Agrawal, A., & Purushothaman, S. S. (2024) · Premier journal of science. · doi:10.70389/pjs.100042
Azmoun, S., Lewis, F., Shoieb, D., Jin, Y., Colicino, E., Mhatre‐Winters, I., Gu, H., Krishnamurthy, H. K., Richardson, J. R., Placidi, D., et al. (2025) · medRxiv · doi:10.1101/2025.05.02.25326824
Self-citationAnadu, V. E., Jimoh-Abdulghaffaar, H. O., Gilbert, T. T., Aneke, O. V., Arietarhire, L. O., Ichipi-Ifukor, P. C., Abdullahi, A. M., Okah, L., Sabine, A. F. Y., Oritsetimeyin, B. U., et al. (2025) · Biology Open · doi:10.1242/bio.061998
Human–Environment Interactions: A Multi-Omics and Interactome Perspective
Kanchan, S., Kesheri, M., Kaithal, P., Srivastava, U., Kaur, H., Pathak, J., & Sinha, R. P. (2025) · Springer eBooks · doi:10.1007/978-981-96-7067-3_12
Role and relation of cell death in Alzheimer’s disease
Hoang, D. A., Le, D. A., Do, T. M. H., & Than, V. T. (2025) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2025.06.024
Mishra, A. K., & Paliwal, S. (2025) · Current Bioactive Compounds · doi:10.2174/0115734072393391250726183450
Nathaniel, M., Dauda, W. P., Abraham, P., Ogra, I. O., Jonathan, E. U., Usman, S., Luka, M. I., Glen, E., Daji, M., Ndukwe, J. K., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-7915450/v1
Apolipoprotein E4 genotype in Moroccan patients with dementia
Razouqi, Y., Bouchikhi, I. E., El‐Abid, H., Mergaoui, M., Khalki, L., & Bouguenouch, L. (2025) · Journal of Neurosciences in Rural Practice · doi:10.25259/jnrp_349_2025
Li, D., Xie, J., Wang, L., Sun, Y., Hu, Y., & Tian, Y. (2023) · Figshare · doi:10.6084/m9.figshare.22614409
Ye, S., Roccati, E., Wang, W., Zhu, Z., Kiburg, K., Huang, Y., Zhang, X., Zhang, X., Liu, J., Tang, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25255773
Therapeutics immunotargets for Tauopathy
Chinnathambi, S., & Rangappa, N. (2025) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2025.10.015
Fikse, E. N., Anderson, F. L., Cho, S., Landry, J., Carloni, E., Biggs, K. E., Paul, K., Daley, T., Chang, T. Y., Kettenbach, A. N., et al. (2026) · Toxicological Sciences · doi:10.1093/toxsci/kfag012
Maladaptive aging trajectory in late-onset Alzheimer's disease
Lv, T., Sun, H., Xia, T., Zhu, M. L., & Li, Y. (2026) · The Innovation Life · doi:10.59717/j.xinn-life.2026.100206
Xue, D., Hirsch, J. A., Besser, L. M., Hughes, T. M., Blue, E. E., Fitzpatrick, A. L., & Fohner, A. E. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71384
Mhatre‐Winters, I., Cirillo, P. M., Factor-Litvak, P. R., Han, Y., Krigbaum, N. Y., Zimmermann, L. M., Link, B. G., Go, Y., Jones, D. P., Cohn, B. A., et al. (2026) · medRxiv · doi:10.64898/2026.05.13.26352896
Self-citationGuilliams, C., & Abner, E. L. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261450630
Small Molecules as Anti-Alzheimer’s Scaffolds
Hazra, R., Roy, S., Gayen, S., Parui, A., Arshad, A., Roy, N., & Sarkar, A. N. (2026) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9798898815646126010013
Zhang, M., Ho, F. K. W., Pell, J. P., Celis-Morales, C., Bailey, M. E. S., Strawbridge, R. J., & Lyall, D. M. (2026) · GeroScience · doi:10.1007/s11357-026-02452-z
Are mouse models of Alzheimer’s disease truly flawed, or are we misusing them?
Calon, F., Otaegui, L., Bouali, M. L., & Hébert, S. S. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.07.069
Oishi, K., Adams, R., Nowrangi, M. A., Zandi, P. P., & Lyketsos, C. G. (2026) · International Review of Psychiatry · doi:10.1080/09540261.2026.2714142
Effect of dietary patterns on biomarkers in Alzheimer’s disease
Rezaeimanesh, N., Khodadadi, S., Montazeri‐Shatouri, R., Motahar, A. A., Hosseini, E., Owji, M., Negah, S. S., & Moghadasi, A. N. (2026) · International review of neurobiology · doi:10.1016/bs.irn.2026.08.012
Cadmium exposure and incidence of all-cause dementia and Alzheimer's disease in US adults
Walker, E., Rodríguez‐Carmona, Y., Wang, X., Mukherjee, B., Merino, L., Hao, W., Dodge, H. H., Albin, R. L., Paulson, H. L., Park, S. K., et al. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261487104
Epigenetics in Alzheimer’s disease: from molecular mechanisms to emerging novel biomarkers
D’Aversa, E., Grisafi, M., Pernagallo, S., Salvatori, F., Singh, A. V., Nucciarone, A., Tisato, V., & Gemmati, D. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1959361
Bednorz, A., & Religa, D. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1933176
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review