Why Alzheimer’s Disease Is So Hard to Treat
Today, the treatment of dementia due to Alzheimer’s disease remains one of the most difficult tasks in medicine. Several existing drugs can only temporarily alleviate symptoms in the early stages of the disease, but do not stop it. Scientists from the UK have unexpectedly discovered that two cancer drugs can not only slow down the progression of the disease, but also partially restore lost brain functions in laboratory animals.
How Two Cancer Drugs Were Linked to Lower Alzheimer’s Risk
Researchers from the University of Cambridge (UK) and the Institute of Dementia Research (UK) studied 1,300 drugs that suppress gene expression – the process of converting information from a section of DNA into RNA or proteins. Having compared this data with electronic records from the University of California on the medical histories of 1.4 million patients aged 65 and over, the scientists calculated that two of them – letrozole and irinotecan – reduce the risk of Alzheimer’s disease by 53.4 and 80.5 percent, respectively, compared with a control group of patients.
However, this data was insufficient. The sample included significantly more women because letrozole was prescribed to women with breast cancer, while irinotecan was usually prescribed to men with colorectal or pancreatic cancer. To experimentally test the effectiveness of letrozole and irinotecan therapy, the scientists conducted experiments on the so-called mouse model of Alzheimer’s disease.
Testing the Drugs in Mice: A Closer Look
Four-month-old mice were divided into four groups: the first group received a placebo, the second – injections of letrozole, the third – irinotecan, the fourth – both drugs. The studies lasted three months, after which the animals underwent behavioral tests. In addition, a histological analysis of the brain was carried out to assess the effect of the drugs on structural changes in the nervous tissue.
Amyloid and Tau Levels Dropped Significantly
All experimental groups (those receiving letrozole, irinotecan, or both drugs) showed a significant reduction in the amount of amyloid plaques in the brain compared to the control group. But the greatest effect was achieved in mice receiving the combination of drugs: the number of amyloid plaques decreased by 30 percent in the letrozole group, by 40 percent in the irinotecan group, and by 60 percent in the combination therapy group. The amount of tau proteins also decreased, but statistically significant values were obtained only in the group treated with both drugs at once.
Mice Also Regained Cognitive Function
Cognitive tests (the rodents had to navigate a maze and remember the route) also showed improvement in the combination therapy group, indicating that lost functions were being restored. Despite the encouraging results, the authors stressed the need for further clinical trials. The effects of the drugs were only analyzed in mouse models of Alzheimer’s disease, which cannot fully reproduce the changes associated with the disease in humans.
The scientists made their conclusions presented in the journal Cell.
Other Studies Also Show a Link Between Cancer Treatment and Alzheimer’s
Interestingly, this is not the first observation that indicates a link between anti-cancer therapy and Alzheimer’s disease. In particular, South Korean scientists recently conducted a cohort study of 70.7 thousand women who had been cured of breast cancer. The incidence of the disease in them was lower than in people of the same sex and age. Scientists assumed that chemotherapy (the risk of Alzheimer’s dropped by 17 percent) and radiotherapy, a treatment that uses ionizing radiation to kill cancer cells (a 23 percent reduction), had a positive effect.
What Causes Alzheimer’s? Still Not Fully Understood
However, the exact causes of Alzheimer’s disease and related dementia are still unknown. For now, the scientific community agrees that pathological changes are associated with the activity of beta-amyloids, which disrupt intercellular connections, and tau proteins, which destroy the transport system of neurons. This assumption was first put forward in the article, published in the journal Nature in 2006. Since then, it has been cited almost two and a half thousand times. However, last summer, the editors retracted the scientific paper due to the revelation falsifications data.
A New Theory: Could Alzheimer’s Be an Autoimmune Disease?
Some researchers suggest, that beta-amyloids are not abnormal proteins, but part of the human immune system. But because of the similarity between the molecules that make up both bacterial membranes and brain cell membranes, beta-amyloid cannot distinguish between bacteria and neurons and attacks the very brain cells it is supposed to protect. Thus, Alzheimer’s disease, which leads to severe dementia, is not a neurodegenerative disease, but an autoimmune disease.
However, the vast majority of scientists continue to believe that the traditional theory of the origin of Alzheimer’s disease is correct and do not share this point of view.
