The cortisol hypothesis and Alzheimer’s disease

Xanamem has been developed in response to evidence that there is a strong association between chronically raised cortisol levels in the blood and in the brain, and the development of Alzheimer’s disease.

Cortisol is more commonly known as the “stress hormone” and is produced in times of physical and mental stress. While this response is quite normal, if cortisol remains elevated for long periods of time, it can become toxic to the neurons (nerve cells) in the brain. Patients with raised cortisol include those with diabetes, with depression, schizophrenia and PTSD, and many patients with Alzheimer’s disease. Interestingly, blood cortisol levels tend to also rise with normal ageing.

Data from several major studies have consistently shown an association between increased cortisol and cognitive decline, together with development of abnormal β-amyloid protein plaques and neurotoxicity in the brain – the hallmarks of Alzheimer’s disease.

Some of the most compelling evidence supporting the cortisol hypothesis was provided by the Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL) study published in early 2017. This study, funded by the CSIRO and several universities and medical research institutes demonstrated that healthy, elderly individuals with high cortisol levels were significantly more likely to develop Alzheimer’s disease than those with low cortisol levels. The study authors concluded that therapies aimed at lowering plasma cortisol levels should be considered as a way to prevent the development of Alzheimer’s disease.

Mechanism of Action

Xanamem blocks the activity of 11β-HSD1, an enzyme that converts inactive cortisone into its active form, cortisol in the brain. Blocking the activity of the enzyme therefore reduces the amount of cortisol in the brain. The enzyme is present in high concentrations in the hippocampus and the frontal cortex, the parts of the brain most associated with recent memory and behaviour, and the regions of the brain most affected by Alzheimer’s disease.

Xanamem was discovered by researchers at the University of Edinburgh in Scotland, and has been under development for over a decade. In late 2014, Actinogen Medical acquired the global rights to Xanamem, with the commitment to actively progress the clinical development of this very promising compound.



In a mouse model of Alzheimer’s disease, Xanamem was effective in improving cognitive function and in clearing amyloid plaques from the brain. The improved cognitive function was observed after only 4 weeks of treatment, and was maintained for at least 41 weeks. If Xanamem can be demonstrated to be as effective in humans, it has the potential to be one of the most meaningful global medical breakthroughs for treating Alzheimer’s disease in decades.


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