The Potential Role of GLP-1 in Alzheimer’s Disease

Exploring GLP-1’s Potential in Cognitive Health

Research suggests that glucagon-like peptide-1 (GLP-1) receptor agonists, traditionally used for managing diabetes and obesity, could hold therapeutic promise for Alzheimer’s disease (AD). These agents exhibit neuroprotective properties that may address core AD pathologies such as amyloid-beta accumulation, tau hyperphosphorylation, and insulin resistance in the brain (Yıldırım Şımşır et al., 2018; Perry et al., 2004).

It’s important to note that GLP-1 receptor agonists are not currently licensed for the treatment of Alzheimer’s disease. However, ongoing research and clinical trials continue to investigate their potential role (Mullins et al., 2019). If you’d like to discuss this emerging therapy further, book a consultation with one of our specialist nurses.

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Mechanisms of GLP-1 in Alzheimer’s Disease

  1. Reduction of Amyloid-Beta Levels: GLP-1 analogs have demonstrated the ability to reduce amyloid-beta plaque formation, a hallmark of AD, through improved insulin signaling and reduced oxidative stress (Bak et al., 2011; Perry et al., 2004).
  2. Prevention of Tau Hyperphosphorylation: Tau protein hyperphosphorylation disrupts neuron function. GLP-1 activation reduces inflammation and supports mitochondrial health to combat this (Perry et al., 2002; Li, 2007).
  3. Improved Brain Insulin Resistance: Insulin resistance in the brain is central to AD pathology. GLP-1 enhances glucose transport across the blood-brain barrier, restoring neuronal function and metabolism (Gejl et al., 2017; Mullins et al., 2019).
  4. Neurogenesis and Synaptic Plasticity: GLP-1 supports neurogenesis and synaptic connectivity, key factors in preserving cognitive function (Perry et al., 2004; Abubakar et al., 2024).

Why Microdosing GLP-1 May Be Beneficial

Microdosing involves starting with lower-than-standard doses, gradually titrated to improve tolerability and reduce side effects. For Alzheimer’s patients, this approach offers:

  • Minimised Side Effects: Microdosing reduces common gastrointestinal issues like nausea (Bak et al., 2011).
  • Better Tolerability: Gradual escalation promotes adherence to the therapy.
  • Early Use in High-Risk Groups: Individuals with mild cognitive impairment (MCI) could benefit from early intervention (Li, 2007).

If you would like to discuss any of the content covered in this blog, please book a consultation with our nurse practitioners.

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Supporting Evidence

  1. Preclinical Models: Animal studies have shown reduced amyloid-beta deposition and improved cognitive performance with GLP-1 therapy (García-Casares et al., 2014; Perry et al., 2002).
  2. Clinical Trials: Mullins et al. (2019) demonstrated improved glucose metabolism in the brain with exenatide, although cognitive benefits were not statistically significant.
    Gejl et al. (2017) found that liraglutide prevented decline in brain glucose metabolism.
  3. Ongoing Research: Studies are investigating combination therapies, such as GLP-1 agonists with DPP4 inhibitors, to enhance neuroprotection (Abubakar et al., 2024).

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Common Q&A about Role of GLP-1 in Alzheimer’s Disease

No, GLP-1 therapies are not currently licensed for Alzheimer’s treatment, but research is ongoing (Mullins et al., 2019; Bak et al., 2011).

GLP-1 enhances brain insulin sensitivity, reduces amyloid-beta plaques, and protects neurons from degeneration (Perry et al., 2004; Gejl et al., 2017).

Microdosing ensures better tolerability, especially for older patients, and may allow earlier intervention (Li, 2007).

Common side effects include nausea and appetite changes, which can be minimised with gradual dosing (Bak et al., 2011; Mullins et al., 2019).

While it cannot reverse the disease, GLP-1 therapy may slow progression and improve early-stage symptoms (Perry et al., 2002; Bak et al., 2011).

Improvements may take weeks to months, depending on individual response and disease stage (Mullins et al., 2019).

Yes, when prescribed under expert supervision, it is generally well-tolerated (Gejl et al., 2017; Li, 2007).

Yes, GLP-1 therapy may complement other medications and lifestyle interventions (Abubakar et al., 2024).

Book a consultation to discuss your needs and suitability for this emerging therapy.

To begin, schedule an initial consultation with our experienced nurse practitioners. During this appointment, we'll assess your medical history, discuss your weight loss goals, and create a personalized microdosing plan tailored to your needs.

References

  1. Yıldırım Şımşır, I., et al. Diabetes & Metabolic Syndrome, 2018. “Glucagon like peptide-1 (GLP-1) likes Alzheimer’s disease.”
  2. García-Casares, N., et al. Revista de neurología, 2014. “[Glucagon-like peptide-1 (GLP-1) mimetics: a new treatment for Alzheimer’s disease?].”
  3. Perry, T., et al. Current Drug Targets, 2004. “A new Alzheimer’s disease interventive strategy: GLP-1.”
  4. Perry, T., et al. Journal of Alzheimer’s Disease, 2002. “The glucagon-like peptides: a new genre in therapeutic targets for intervention in Alzheimer’s disease.”
  5. Bak, A.M., et al. Expert Opinion on Therapeutic Targets, 2011. “Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer’s disease and diabetes.”
  6. Mullins, R.J., et al. Current Alzheimer Research, 2019. “Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimer’s disease.”
  7. Gejl, M., et al. Scientific Reports, 2017. “Blood-Brain Glucose Transfer in Alzheimer’s disease: Effect of GLP-1 Analog Treatment.”
  8. Li, L., Neuroscience Bulletin, 2007. “Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer’s disease?.”
  9. Abubakar, M.D., et al. Current Topics in Medicinal Chemistry, 2024. “GLP-1/GIP Agonist as an Intriguing and Ultimate Remedy for Combating Alzheimer’s Disease through its Supporting DPP4 Inhibitors: A Review.”
  10. Perry, T., et al. Current Alzheimer Research, 2005. “Enhancing central nervous system endogenous GLP-1 receptor pathways for intervention in Alzheimer’s disease.”