ArticlePloS one2016
Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer's disease models: a systematic review and meta-analysis of preclinical studies.Frontiers in pharmacology · 2023Pooled it
- Glucagon-Like Peptide-1 Signaling in Learning and Memory: Evidence, Mechanisms, and Therapeutic Implications.Biological psychiatry · 2026Review
- Elevated endogenous glucagon-like peptide-1 as a novel Alzheimer's disease biomarker associated with neuroinflammation and Aβ pathology.General psychiatry · 2026Article
- 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
- 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
- Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders.Nature aging · 2026Review
- GLP-1 and the Degenerating Brain: Exploring Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Incretin-Based Therapies in Alzheimer's and Parkinson's Disease: Advancing Neuroprotection With Dual and Triple Agonists-A Review.Health science reports · 2025Article
- Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Role of glucagon-like peptide-1 receptor agonists in Alzheimer's disease and Parkinson's disease.Journal of biomedical science · 2024Review
- The GLP-1 medicines semaglutide and tirzepatide do not alter disease-related pathology, behaviour or cognitive function in 5XFAD and APP/PS1 mice.Molecular metabolism · 2024Article
- Crosstalk between Alzheimer's disease and diabetes: a focus on anti-diabetic drugs.Metabolic brain disease · 2023Review
- The Late Stage of Abnormal Aging: Dementia.Advances in experimental medicine and biology · 2023Article
- Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment.Pharmacological research · 2022Review
- Brain energy failure in dementia syndromes: Opportunities and challenges for glucagon-like peptide-1 receptor agonists.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Review
- Protective properties of GLP-1 and associated peptide hormones in neurodegenerative disorders.British journal of pharmacology · 2022Review
- The Effects of Moxibustion on Learning and Memory and m6A RNA Methylation in APP/PS1 Mice.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer's disease.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the major histopathological hallmarks of Alzheimer's disease (AD) is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1) receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP) and presenilin-1 (PS1) are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E) and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9) of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c.), or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.). In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.
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