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Cited by 21Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Dimethyl fumarate does not mitigate cognitive decline and β-amyloidosis in female APPPS1 mice

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Möhle, Luisa, Brackhan, Mirjam, Bascuñana, Pablo, Pahnke, Jens·2021·Brain Research
DOI 10.1016/j.brainres.2021.147579
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Abstract

Introduction Alzheimer's disease (AD) is the leading cause of dementia and a major global health issue. Currently, only limited treatment options are available to patients. One possibility to expand the treatment repertoire is repurposing of existing drugs such as dimethyl fumarate (DMF). DMF is approved for treatment of multiple sclerosis and previous animal studies have suggested that DMF may also have a beneficial effect for the treatment of AD. Methods We used an APPPS1 transgenic model of senile β-amyloidosis and treated female mice orally with DMF in two treatment paradigms (pre and post onset). We quantified learning and memory parameters, β-amyloidosis, and neuroinflammation to determine the potential of DMF as AD therapeutics. Results Treatment with DMF had no influence on water maze performance, β-amyloid accumulation, plaque formation, microglia activation, and recruitment of immune cells to the brain. Compared to vehicle-treated animals, oral DMF treatment could not halt or retard disease progression in the mice. Discussion Our results do not favour the use of DMF as treatment for AD. While our results stand in contrast to previous findings in other models, they emphasize the importance of animal model selection and suggest further studies to elucidate the mechanisms leading to conflicting results.

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  • The drugs with evidence of little to no effect on AD risk included lipid-lowering agents (ezetimibe, mipomersen, and statins), antihypertensives, dimethyl fumarate, and drugs commonly used in treatment of rheumatoid arthritis (tofacitinib, tocilizumab, and TNF inhibitors).

    “These drugs included lipid-lowering agents (ezetimibe, mipomersen, and statins) (Williams et al., 2020), antihypertensives (Walker et al., 2020), dimethyl fumarate (approved for the treatment of multiple sclerosis) (Möhle et al., 2021), and drugs commonly used in treatment of rheumatoid arthritis (tofacitinib, tocilizumab, and TNF inhibitors) (Desai et al., 2022).”

    From Drug repurposing for Alzheimer’s disease from 2012–2022—a 10-year literature review (2023) · cites this paper as Möhle et al., 2021

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Metadata

Authors
Möhle, L., Brackhan, M., Bascuñana, P., & Pahnke, J.
Affiliations
Oslo University Hospital (NO)
Corresponding author
  • Möhle, Luisa
  • Pahnke, Jens
ORCID
Venue
Brain Research
Publisher
Elsevier BV
Published
2021-10
Volume
1768
Pages
147579
ISSN
0006-8993 (ISSN-L)
DOI
10.1016/j.brainres.2021.147579
OpenAlex
W3180511953
Cited by
21
References
4
Citations by year
2026: 1 · 2025: 1 · 2024: 10 · 2023: 5 · 2022: 4
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • European Environment Agency (TAČR TARIMAD TO100078)
  • Deutsche Forschungsgemeinschaft
  • Agence Nationale de la Recherche (2020–02905)
  • Nasjonalforeningen for Folkehelsen (16154)
  • EU Joint Programme – Neurodegenerative Disease Research (301228)
  • European Commission
  • Helse Sør-Øst RHF (2019054, 2019055)
  • Ministerium für Wissenschaft und Wirtschaft, Land Sachsen-Anhalt (ZS/2016/05/78617)
  • EEA Grants and Norway Grants
  • Horizon 2020 Framework Programme (643417)
  • Bundesministerium für Bildung und Forschung (01ED1605, 2015-06795, 30000-12631, 882717)
  • Latvijas Zinātnes Padome
  • Norges forskningsråd (260786, 295910, 327571)
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
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
dimethyl fumarate, Alzheimer's disease, drug repurposing, beta-amyloidosis, cognitive decline, learning and memory, neuroinflammation, microglial activation, female mice, animal model selection, disease-modifying therapy
MeSH terms
Dimethyl Fumarate, Neuroinflammatory Diseases, Alzheimer Disease, Amyloidosis, Animals, Brain, Disease Models, Animal, Female, Hippocampus, Humans, Inflammation, Mice, Transgenic, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Cognitive Dysfunction

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