Mounjaro and the Brain (Alzheimer’s and Parkinson’s)

“Currently, there is no disease-modifying treatment available for Alzheimer’s and Parkinson’s disease (AD and PD) and that includes the highly controversial approval of the Aβ-targeting antibody aducanumab for the treatment of AD. Hence, there is still an unmet need for a neuroprotective drug treatment in both AD and PD. Type 2 diabetes is a risk factor for both AD and PD. Glucagon-like peptide 1 (GLP-1) is a peptide hormone and growth factor that has shown neuroprotective effects in preclinical studies, and the success of GLP-1 mimetics in phase II clinical trials in AD and PD has raised new hope. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. GLP-1 analogs are safe, well tolerated, resistant to desensitization and well characterized in the clinic. Herein, we review the existing evidence and illustrate the neuroprotective pathways that are induced following GLP-1R activation in neurons, microglia and astrocytes. The latter include synaptic protection, improvements in cognition, learning and motor function, amyloid pathology-ameliorating properties (Aβ, Tau, and α-synuclein), the suppression of Ca2+ deregulation and ER stress, potent anti-inflammatory effects, the blockage of oxidative stress, mitochondrial dysfunction and apoptosis pathways, enhancements in the neuronal insulin sensitivity and energy metabolism, functional improvements in autophagy and mitophagy, elevated BDNF and glial cell line-derived neurotrophic factor (GDNF) synthesis as well as neurogenesis. The many beneficial features of GLP-1R and GLP-1/GIPR dual agonists encourage the development of novel drug treatments for AD and PD.”

The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease: An in-depth review

Frontiers in Neuroscience, September 2022

Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function

Frontiers in Pharmacology August, 2020 


“The higher prevalence of depression and other mood disorders in obese patients and negative effects on mood of previously avail- able anti-obesity treatments highlight the need for experimental studies on the impact on mood of newly emerging obesity treat- ments. Here we show that GLP-1R activation, a recently approved anti-obesity treatment, induces anxiety immediately after the com- mencement of the treatment, this anxiety subsides with chronic treatment and is in fact replaced by positive effects on mood mani- fested by reduced depression-like behavior. These results may have direct relevance to the clinic, and indicate that EX4 may be espe- cially useful for those obese patients manifesting with comorbid depression.”

GLP-1 is both anxiogenic and antidepressant; divergent effects of acute and chronic GLP-1 on emotionality

Psychoneuroendocrinology August 2015


Insights into a possible role of glucagon-like peptide-1 receptor agonists in the treatment of depression

Pharmacological Reports, 2021