Alzheimer’s disease affects 50 million people worldwide and just like any modern lifestyle disease, it is steadily increasing. Unfortunately, a cure has not yet been found, despite decades of research. The pathophysiology of Alzheimer’s disease is extraordinarily complex and involves many different factors. Despite it being a protein misfolding disease, a lot of evidence currently point to insulin resistance, impaired glucose metabolism and comorbidities with other metabolic disorders such as obesity, elevated blood lipids, and non-alcoholic fatty liver disease, as a potential root cause. Genetics aside, it seems like poor metabolic functioning affects the brain and central nervous system a great deal: affecting mood, behaviour, and cognitive performance. Even mood disorders are interlinked with metabolic disorders and increase the risk for Alzheimer’s disease later in life. This is a summary of objectively chosen original research articles, published between 2011-2021 and with insulin resistance as the main objective for cognitive impairment and Alzheimer’s disease.

This review article focuses on the use of infectious bacteria as delivery tool for tumour necrosis factor α (TNF-α), a well-studied cytokine, in the context of immunotherapy for cancer treatment. The tumour targeting properties of certain bacteria strains has been known for decades as well as the tumour catabolizing effect of TNF-α. The combination of these two have been studied in murine models for various types of cancer with promising results. Research in this fascinating field is unfortunately uncommon, thus the number of high-quality articles is limited. Search was done via Google Scholar in combination with PubMed, to increase the coverage and find peer-reviewed, original, and primary research articles.

Key findings show that attenuated or genetically modified species of bacteria have fewer side effects and can be effective in delivering cytokines to tumour sites. TNF-α is produced by macrophages/monocytes during acute inflammation or infection, thus can be triggered by infectious bacteria which in turn induce apoptosis. The cytotoxic effect of the bacteria can be enhanced with localized irradiation. Promising results have been shown in bladder, breast, colon, glial, lung, ovarian, pancreatic, prostate, and renal cancer cells.

The need for better, safer, and more effective cancer treatment is apparent as traditional chemotherapy and radiation can cause a lot of harm for the patient, and not necessarily prolong the lifespan. The success-rate for these treatments vary greatly depending on the type of cancer, but for tumours that cannot be surgically removed the outcome is generally quite poor. A drawback of chemotherapy is that tumours can grow resistant to the treatment while healthy cells continue to be exposed, increasing the risk of severe side effects. Different types of biological therapies are a modern and possibly safer approach, even though immunotherapy comes with substantial risks. Using the innate immune system to fight tumour cells is not always safe, because uncontrolled and excessive release of pro-inflammatory signalling molecules can result in multisystem organ failure and death. This phenomenon is called cytokine release syndrome (cytokine storm) and is one of the major risks of immunotherapy. However, tailored biological therapies have proven their effectiveness for a wide range of cancer types, and the next step in this evolution is to genetically engineer both delivery systems and mechanisms of action. This approach can be combined with the traditional radiation and chemotherapy for increased effectiveness, even if biological therapies as a stand-alone treatment, can be a goal for the future.