Alzheimer’s disease—the most common form of dementia—is an irreversible, progressive disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks. It’s currently ranked as the sixth leading cause of death in the United States, but recent estimates indicate that the disorder may rank third, just behind heart disease and cancer, as a cause of death for older people.
Gerontologist Laura Wayman says: “I tell family caregivers that they need to start thinking of a loved one’s brain like a piece of Swiss cheese, which has random holes in it. The disease is robbing them of brain cells that allow them to function normally.” She explains that when a person with Alzheimer’s tries to access the functionality of their brain, they may either access “cheese” (a lucid moment), or a “hole” (a confused moment in which they frantically try to compensate for memory loss with bizarre behaviors, often linked to feelings and memories from their past).
Greg O’Brien, author of “On Pluto: Inside the Mind of Alzheimer’s,” and a patient-advocate for the Alzheimer’s Association, is documenting his own Alzheimer disease while he still can: “Daily medications serve to slow down the progression of the disease and to help control the rage on days when 60 percent of my short-term memory is gone in 30 seconds—days when I hurl the phone across the room, a perfect strike to the sink, because in the moment I don’t remember what number to dial. Or when I smash the lawn sprinkler against an oak tree in the back yard because I can’t recall how it works, or when I push open the flaming-hot glass door to the wood stove in the family room bare-handed to stoke the fire because my mind told me it was a good idea, resulting in a second-degree burn. Or simply when I cry privately, the tears of a little boy, because I fear that I’m alone, nobody cares and the innings are beginning to fade.”
According to the National Institute on Aging, during the very early stage of disease, people with Alzheimers’ disease do not show any symptoms—however, during this time, several changes take place in the brain. Abnormal deposits of proteins form amyloid plaques and tau tangles throughout the brain. Consequently, once-healthy neurons begin to work less efficiently. Amyloid plaques are the build up of sticky proteins called beta amyloid, and tau tangles are twisted strands of a protein called tau. Over time, neurons lose their ability to function and communicate with each other, and eventually die. Before long, the damage spreads to a nearby structure in the brain called the hippocampus, which is essential in forming memories. As more neurons die, affected brain regions begin to shrink. By the final stage of Alzheimer’s disease, damage is widespread, and brain tissue has shrunk significantly.
Although there are medicines that can ameliorate symptoms of the disease, there is no known cure for Alzheimer’s disease. Now, results from a new study carried out in a mouse model indicate that a cytokine called interleukin-33 (IL-33) can reverse Alzheimer’s disease-like pathology and cognitive decline. The study (IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline) was published a few days ago (April 18, 2016) in the journal Proceedings of the National Academy of Sciences USA.
Eddy Liew, one of the study authors, said in a press release: “IL-33 is a protein produced by various cell types in the body and is particularly abundant in the central nervous system (brain and spinal cord). We carried out experiments in a strain of mouse (APP/PS1) which develop progressive Alzheimer’s-like disease with ageing. We found that injection of IL-33 into aged APP/PS1 mice rapidly improved their memory and cognitive function to that of the age-matched normal mice within a week.”
IL-33 appears to work by mobilizing microglia—the primary immune cells of the central nervous system. These cells are highly similar to peripheral macrophages. They act as the major inflammatory cell type in the brain, and respond to infectious microbes and injury by becoming “activated”—a process whereby they rapidly change morphology, proliferate and migrate to the site of infection/injury where they engulf and destroy infectious microbes as well as remove damaged cells.
According to the new study, microglia surround the amyloid plaques, take them up and digest them, thus reducing their number and size. In addition, the study results show that IL-33 treatment inhibits inflammation in brain tissue—inflammation has been shown earlier to potentiate plaque and tangle formation. Therefore, IL-33 not only helps to clear the amyloid plaque already formed, but also prevents the deposition of plaques and tangles.
How do these results obtained in mice relate to humans? Previous research suggests that IL-33 may play a role in the development of Alzheimer’s disease in humans—genetic studies show an association between IL-33 mutations and Alzheimer’s disease in European and Chinese populations. Furthermore, the brain of patients with Alzheimer’s disease contains less IL-33 than the brain from non-Alzheimer’s patients.
However, Liew added: “Exciting as it is, there is some distance between laboratory findings and clinical applications. There have been enough false ‘breakthroughs’ in the medical field to caution us not to hold our breath until rigorous clinical trials have been done. We are just about entering Phase I clinical trial to test the toxicity of IL-33 at the doses used. Nevertheless, this is a good start.”