The effect of AMPK activation on Alzheimer's-like symptoms in APP mice
Abstract
Research toward understanding Alzheimer's disease has revealed that it is strongly linked with metabolic dysfunction, such as that found in Type II Diabetes. For instance, diabetic patients have a doubled risk of developing AD, while Alzheimer's patients have disrupted insulin signaling in the brain. Moreover, some lifestyle modifications beneficial to diabetic patients - specifically, increased physical activity and caloric restriction - have shown promise as tools to manage AD. Both of these interventions create an energy deficit whereby the cellular energy sensor AMPK becomes activated. In turn, AMPK activation promotes energy availability, insulin sensitivity and cellular survival during times of stress. We activated AMPK both pharmacologically and genetically in a transgenic mouse model of AD and measured the effect on learning and memory function by the Morris water maze. Surprisingly, our results revealed a gender- specific response in Alzheimer's phenotypes. Pharmacological activation of AMPK by the anti-diabetic drug metformin in male APP mice worsened learning and memory function. This finding was reproduced with a genetic model of AMPK activation, requiring only liver- specific activity to occur. Remarkably, activation of AMPK in this murine model, either by genetic means or metformin treatment, had beneficial effects for female animals. The results herein demonstrate the effect of AMPK activation in the APP mouse model of AD, the gender-specific differences in…
How strong is the evidence?
Evidence Hub reads this as a thesis, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.