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Use of Caenorhabditis elegans as a model to study Alzheimer’s disease and other neurodegenerative diseases
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Advances in research and technology has increased our quality of life, allowed us to combat diseases, and achieve increased longevity. Unfortunately, increased longevity is accompanied by a rise in the incidences of age-related diseases such as Alzheimer's disease (AD). AD is the sixth leading cause of death, and one of the leading causes of dementia amongst the aged population in the USA. It is a progressive neurodegenerative disorder, characterized by the prevalence of extracellular Aβ plaques and intracellular neurofibrillary tangles, derived from the proteolysis of the amyloid precursor protein (APP) and the hyperphosphorylation of microtubule-associated protein tau, respectively. Despite years of extensive research, the molecular mechanisms that underlie the pathology of AD remain unclear. Model organisms, such as the nematode, Caenorhabditis elegans, present a complementary approach to addressing these questions. C. elegans has many advantages as a model system to study AD and other neurodegenerative diseases. Like their mammalian counterparts, they have complex biochemical pathways, most of which are conserved. Genes in which mutations are correlated with AD have counterparts in C. elegans, including an APP-related gene, apl-1, a tau homolog, ptl-1, and presenilin homologs, such as sel-12 and hop-1. Since the neuronal connectivity in C. elegans has already been established, C. elegans is also advantageous in modeling learning and memory impairments seen during AD. This article addresses the insights C. elegans provide in studying AD and other neurodegenerative diseases. Additionally, we explore the advantages and drawbacks associated with using this model.
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“The most notable example is the lack of Aβ in Drosophila and C. Elegans [1, 38].”
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eQTL mapping in transgenic alpha-synuclein carrying Caenorhabditis elegans recombinant inbred linePreprint
Huang, Y., Wang, Y. A., van Sluijs, L., Vogels, D. H. J., Chen, Y., Tegelbeckers, V. I. P., Schoonderwoerd, S., Riksen, J. A. G., Kammenga, J. E., Harvey, S. C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.18.553811
Mishra, R., Joykutty, L., & Oyarbide, K. (2019) · Journal of Emerging Investigators · doi:10.59720/19-018
Holcom, A., Fuentealba, M., Sivapatham, R., King, C. D., Osman, H., Foulger, A., Bhaumik, D., Schilling, B., Furman, D., Andersen, J. K., et al. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4588112
Gut Microorganisms and Caenorhabditis elegans: A Model for Microbiome Research
Mallick, S., Pradhan, J., Raturi, A., Daimai, C., & Negi, V. D. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13320-6.00034-2
A Sideroflexin/Connexin adaptor ties kinesin-3 to mitochondria in neuronsPreprint
Barmaver, S. N., Bayansan, O., Khawaja, M. S., Ruckmani, V. M., Putri, D. S., Shanmugam, M. M., & Wagner, O. I. (2024) · Research Square · doi:10.21203/rs.3.rs-2953132/v2
Caenorhabditis elegans models of tauopathy
Hady, B. H. A. E., & Mohsen, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-16128-5.00015-3
DARG: a Database of Alzheimer Related Genes in Model OrganismsPreprint
Song, J. Y., Zhou, E., & Hu, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.29.635533
Oluwatunase, G. O., Okwute, P. G., Asafa, O. O., Oyeniran, D. A., & Ogenetega, O. B. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1008845
Anticonvulsant effects of novel and repurposed drugs on docetaxel-induced neuropathy in C. elegansPreprint
Gonzalez-Lerma, P., Lloyd, C., Park, S. J., & Dawson-Scully, K. D. (2025) · Research Square · doi:10.21203/rs.3.rs-6372250/v1
Investigations of forgetting in Caenorhabditis elegans
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Paul, F., Castro, A. C. T., Costa, M. D., Lindsay, V., Fiúza-Fernandes, J., Goua, M., Bermano, G., Russell, W., Maciel, P., & Kong Thoo Lin, P. (2019) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Explosive shock wave exposure leads to age-accelerated motor and sensory decline in C. elegansPreprint
Tittelmeier, J., Seeber, H., Grasse, D., Barapatre, N., Schmitz, C., Krentel, D., Grobert, S., & Nussbaum-Krammer, C. I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.19.695190 · Cited by 1
SFXN-1.2-CX32 complex selectively recruits UNC-104 to neuronal mitochondriaPreprint
Barmaver, S. N., Bayansan, O., Khawaja, M. S., Ruckmani, V. M., Putri, D. S., Shanmugam, M. M., & Wagner, O. I. (2026) · Research Square · doi:10.21203/rs.3.rs-2953132/v3
Multilevel-prompt foundation model for nematode instance segmentation
Wang, N., Shu, Z., Xu, J., Zhong, R., Wang, H., Xu, L., Guo, L., Sun, Y., & Li, Y. (2026) · Measurement Science and Technology · doi:10.1088/1361-6501/ae46b3
Metadata
- Authors
- Alexander, A. G., Marfil, V., & Li, C.
- Affiliations
- The Graduate Center, CUNY (US)
- City College of New York (US)
- Corresponding author
- Li, Chris
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2014-09-05
- Volume
- 5
- Pages
- 279-279
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC4155875
- OpenAlex
- W1983814182
- Cited by
- 310
- References
- 322
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 38 · 2023: 42 · 2022: 40 · 2021: 35 · 2020: 39 · 2019: 19 · 2018: 23 · 2017: 14 · 2016: 20 · 2015: 6 · 2014: 1
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CUNY Academic Works (City University of New York) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation
- National Institutes of Health
- National Institute on Aging (R01AG032042)
- National Institute of General Medical Sciences (R25GM056833)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Alzheimer's disease, Caenorhabditis elegans, neurodegenerative diseases, amyloid plaques, neurofibrillary tangles, amyloid precursor protein, tau hyperphosphorylation, presenilin, learning and memory impairment
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.
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