Dimethyl fumarate does not mitigate cognitive decline and ß-amyloidosis in female APPPS1 mice.
Brain Res
; 1768: 147579, 2021 10 01.
Article
em En
| MEDLINE
| ID: mdl-34233173
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 ß-amyloidosis and treated female mice orally with DMF in two treatment paradigms (pre and post onset). We quantified learning and memory parameters, ß-amyloidosis, and neuroinflammation to determine the potential of DMF as AD therapeutics.RESULTS:
Treatment with DMF had no influence on water maze performance, ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Disfunção Cognitiva
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Fumarato de Dimetilo
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Amiloidose
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Brain Res
Ano de publicação:
2021
Tipo de documento:
Article
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
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NL
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PAISES BAJOS
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THE NETHERLANDS