Rapamycin as a potential treatment for Alzheimer’s disease

A drug that has been touted to help you live as long as possible may be the key to treating Alzheimer’s. Rapamycin as a potential treatment for Alzheimer’s disease has been eyed by scientists, who are now investigating.

What is rapamycin?

Rapamycin is a drug initially developed to prevent organ rejection in organ transplant recipients. Recently, it has been recognized as a potential antiaging drug since it slows down the aging process in animal model studies [1].

First isolated from a bacterium in 1972, rapamycin is now seen to have many uses. Rapamycin is derived from Rapa Nu, the bacteria found on Easter island. 

This drug has been shown to increase the lifespan of flies and mice. For instance, one animal model study [2] has demonstrated that rapamycin increases the lifespan of different strains of mice by 10 to 30% when started either late or early in life and when administered transiently, intermittently or continuously.

Notably, recent animal model studies even showed that rapamycin treatment for at least three months resulted in a 60% increase in the lifespan of the mice. 

Interestingly, these animal model studies likewise revealed that rapamycin reverses or delays age-related decline and diseases such as:

Rapamycin as a potential treatment for Alzheimer’s disease 

Alzheimer’s disease (AD) affects at least 5.4 million people in the US alone. The burden associated with caring for an individual with AD is high, with family caregivers or carers admitting feelings of isolation, loneliness, fear and anxiety.

Due to the aging of the US population, it is projected that at least 13.8 million people will have developed dementia by 2050. 

Rapamycin as a potential treatment for Alzheimer's
Photograph: LightFieldStudios/Envato

Since age remains the primary factor in developing AD, this disease is projected to strain the healthcare system of countries with aging populations. There is still no effective treatment to prevent AD or its progression.

Several factors have been identified to cause the delay in finding an effective treatment for the disease. These include the complexity of the molecular mechanisms of AD and the limited ability to predict the onset of this condition at an earlier stage where management is likely to still be effective. 

Another factor related to delay in AD treatment is the lack of attention on the aging process linked to AD development. Animal model studies have shown that slowing the aging process is also related to delaying the progression of dementia.

Hence, it is hypothesized that targeting the aging process might reduce the risk of dementia or prevent the onset of this condition. 

These animal model studies have shown that rapamycin can initiate the following: 

  • Reducing amyloid-beta deposition (amyloid-beta peptides have been implicated as the primary cause of dementia or AD in 50-60% of cases) 
  • Reducing neurofibrillary tangles 
  • Preserving blood-brain barrier
  • Restoring cerebral blood flow 
  • Restoring cerebral microvascular density 
  • Improving cognitive function 
  • Preventing tau-induced neuronal loss 

Patients with AD develop amyloid-beta deposits

Although not fully understood, it is hypothesized that the presence of amyloid-beta deposits in the brain leads to AD development. These proteins are sticky and present as starch-like plaques in those with AD.

One possible explanation for why these plaques cause AD is these deposits’ disruption of the synapsis in the brain. Researchers have found that the greater the number of amyloid-beta deposits, the greater the cognitive impairment. 

A common view is that beta-amyloid protein fragments are destroyed and eliminated in normal brains. However, these protein fragments accumulate in patients with AD and form into plaques [4]. 

Meanwhile, neurofibrillary tangles are described as an abnormal accumulation of tau proteins inside the neurons. In contrast, neurons of healthy brains contain microtubules that guide the passage of molecules and nutrients from the neuron’s cell body to the dendrites and axons [5]. 

Alzheimer’s Disease: Tau proteins detach from the microtubules

When the neurons are healthy, the tau proteins usually bind to the microtubules inside the neurons to stabilize these structures. However, in AD, these tau proteins detach from the microtubules and stick to other tau proteins forming threads and, later, tangles inside the neurons. 

When these tangles accumulate, the transport of molecules and nutrients from the cell body to the dendrites and axons is affected. In turn, this harms the ability of the neurons to communicate with each other. 

In AD, the brain changes consist of beta-amyloid plaque deposition and increased density of neurofibrillary tangles. The accumulation of these neurofibrillary tangles is concentrated in brain areas involved with memory. 

In addition, restoring cerebral blood flow is necessary for optimal brain functioning. Since rapamycin also improves the blood-brain barrier, it protects the brain from toxic and harmful substances and provides the optimal flow of nutrients into the brain.

Restoration of the cerebral microvascular density also ensures that the brain receives sufficient nutrients and oxygen, preventing early degeneration of the brain cells. 

Human studies on rapamycin and Alzheimer’s Disease

Considering the overwhelming evidence from animal model studies on rapamycin as a potential treatment of Alzheimer’s Disease, clinical trials must be conducted to determine if the same findings from animal model studies are also seen in human studies. 

Currently, a phase 2 study [6] examining the safety and effects of rapamycin in treating mild cognitive impairment in adults with early-stage AD is underway. 

Rapamycin in treating cognitive impairment
Photograph: DC Studio/Envato

What are the potential side effects of rapamycin? 

There is still little data on the side effects of rapamycin on older individuals.

A study [7] that included older adults and examined the effects of rapamycin on cognitive function, immune status and physical performance found that the drug has relatively mild effects and has no adverse effects or impacts on insulin sensitivity, insulin secretion and changes in blood glucose when given for eight weeks. 

Adults with cancer and those receiving an organ transplant reported mild side effects of rapamycin, including:

  • Nausea
  • Diarrhea
  • Mouth sores

It should be noted that these patients were immunocompromised and taking other medications along with rapamycin. These findings show that rapamycin would not lead to serious side effects in the older adult population with AD. 

When is the best time to administer rapamycin for AD? 

From available data, early intervention is still crucial in delaying AD progression. When applied to AD, treatment with rapamycin would have to start in the early stages of the disease to optimize its effects.

However, it is also hypothesized that since rapamycin can improve cardiac and immune function, it could also improve AD symptoms in those with a moderate stage of the disease. 

Take-home message 

Rapamycin is an immunosuppressant drug used to help patients undergoing organ transplantation. Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved rapamycin as an immunosuppressant agent.

Apart from being an immunosuppressant, there is growing evidence that it can delay aging and improve immune and cardiac function.

Recently, animal model studies have suggested that rapamycin effectively prevents and slows AD progression in animal model studies. It can reduce neurofibrillary tangles and amyloid-beta plaques, which are hallmarks of AD in humans. 

To date, a recent phase 2 clinical trial is being conducted to examine the effects of this drug in treating AD in patients with mild cognitive impairment. This drug may potentially treat AD in the early to mild stages.

Since the results of this clinical trial are not yet available, relying on the results of animal model studies would reveal the potential of this drug in reducing symptoms of AD. 

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814615/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786175/ 
[3] https://pubmed.ncbi.nlm.nih.gov/27304501/ 
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844114/ 
[5] https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease 
[6] https://www.alzheimers.gov/clinical-trials/rapamycin-mild-cognitive-impairment-and-early-stage-alzheimers-disease 
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869166/ 

Photograph: LightFieldStudios/Envato
The information included in this article is for informational purposes only. The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.