ArticleMolecular metabolism2024
The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice.
Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Genetic evidence supports a cortical neuroprotective role of GLP-1 receptor activation in Alzheimer's disease: A drug-target Mendelian randomization study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Elevated endogenous glucagon-like peptide-1 as a novel Alzheimer's disease biomarker associated with neuroinflammation and Aβ pathology.General psychiatry · 2026Article
- Glucose-Lowering Therapies and Cognitive Decline: From Molecular Mechanisms to Clinical Evidence and Future Perspectives.Advances in therapy · 2026Review
- Semaglutide as a potential neuroprotective agent for neurological and neurodegenerative disorders: Mechanisms, preclinical evidence, and translational challenges and opportunities.Molecular biology reports · 2026Review
- The Neuroprotective Potentials of Dual GIP/GLP1-RA (Tirzepatide): From Preclinical Experiments to Clinical Trials: A Scoping Review.Brain and behavior · 2026Article
- GLP-1 receptor agonists, metabolic syndrome, and Alzheimer's disease: Lessons and opportunities from the EVOKE trials.Journal of neuroendocrinology · 2026Review
- Preventative semaglutide and tirzepatide treatment does not alter disease progression in the 5xFAD mouse model of Alzheimer's disease.Cell reports. Medicine · 2026Article
- Semaglutide Selectively Improves Metabolic and Cognitive Function in 5xFAD Mice.International journal of molecular sciences · 2026Article
- Impact of Semaglutide on Hippocampal Injury in a Streptozotocin-Induced Model of Alzheimer's Disease.Biomedicines · 2026Article
- Tirzepatide attenuates neurotoxicity by suppressing inflammation, apoptosis and restoring neurotrophin expression in an Alzheimer's disease-like rat model.Metabolic brain disease · 2026Article
- Sleeve gastrectomy improves metabolic health, cognition, and Alzheimer's Disease pathology in 3xTG mice.bioRxiv : the preprint server for biology · 2026Article
- Complementary neuroprotective effects of semaglutide and papaya in diabetic encephalopathy via antioxidant and insulin-signaling pathways.Scientific reports · 2026Article
- Beyond diabetes and obesity: GLP-1 receptor agonists in disrupting the vicious cycle of metabolic dysfunction and neuroinflammation.Diabetes, obesity & metabolism · 2026Review
- The promise of GLP-1 receptor agonists for neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- Potential Neuroprotective Role of GLP-2 in Alzheimer's Disease: Clinical Observations, Mechanistic Insights, and Comparison with GLP-1.International journal of molecular sciences · 2026Article
- Targeting neuroinflammation in neurodegenerative disorders: the emerging potential of semaglutide.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Semaglutide in cognitive dysfunction: neuroprotective potential, clinical trial limitations, and a prevention-focused framework.Frontiers in aging neuroscience · 2026Review
- GLP-1 and GIP class drugs have neuroprotective properties in Alzheimer's and Parkinson's disease.Frontiers in neuroscience · 2026Review
- The novel GLP-1/GIP dual receptor agonist DA5-CH is superior to tirzepatide and exendin-4 in the 6-OHDA Parkinson rat model.Frontiers in endocrinology · 2026Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe development of glucagon-like peptide-1 receptor (GLP-1R) agonists for the treatment of type 2 diabetes and obesity has been accompanied by evidence for anti-inflammatory and cytoprotective actions in the heart, blood vessels, kidney, and brain. Whether GLP-1R agonists might be useful clinically for attenuating deterioration of cognitive dysfunction and reducing the progression of Alzheimer's disease remains uncertain.
methodsHere we evaluated the actions of semaglutide and tirzepatide, clinically distinct GLP-1 medicines, in two mouse models of neurodegeneration.
resultsSemaglutide reduced body weight and improved glucose tolerance in 12-month-old male and female 5XFAD and APP/PS1 mice, consistent with pharmacological engagement of the GLP-1R. Nevertheless, amyloid plaque density was not different in the cerebral cortex, hippocampus, or subiculum of semaglutide-treated 12-month-old 5XFAD and APP/PS1 mice. IBA1 and GFAP expression were increased in the hippocampus of 5XFAD and APP/PS1 mice but were not reduced by semaglutide. Moreover, parameters of neurobehavioral and cognitive function evaluated using Open Field testing or the Morris water maze were not improved following treatment with semaglutide. To explore whether incretin therapies might be more effective in younger mice, we studied semaglutide and tirzepatide action in 6-month-old male and female 5XFAD mice. Neither semaglutide nor tirzepatide modified the extent of plaque accumulation, hippocampal IBA1+ or GFAP+ cells, or parameters of neurobehavioral testing, despite improving glucose tolerance and reducing body weight. mRNA biomarkers of inflammation and neurodegeneration were increased in the hippocampus of male and female 5XFAD mice but were not reduced after treatment with semaglutide or tirzepatide.
conclusionsCollectively, these findings reveal preservation of the metabolic actions of two GLP-1 medicines, semaglutide and tirzepatide, yet inability to detect improvement in structural and functional parameters of neurodegeneration in two mouse models of Alzheimer's disease.
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