In July 2022, the journal Science reported that a landmark 2006 research paper published in the prestigious journal Nature, in which the beta-amyloid protein was identified as the cause of Alzheimer's disease, may have been based on fabricated data.
A year earlier, in June 2021, the U.S. Food and Drug Administration approved aducanumab, an antibody targeting beta–amyloid, as a treatment for Alzheimer's disease, although data confirming its use were incomplete and contradictory. Some experts believe that aducanumab should not have been approved, while others argue that it should be given a chance.
Why are researchers still unable to find a cure for one of the most important diseases facing humanity, given that millions of people need effective treatment?
Moving away from the beta-amyloid paradigm
For many years, scientists have been focused on trying to develop new treatments for Alzheimer's disease, preventing the formation of brain-damaging accumulations of this protein. In fact, scientists may have gotten into some kind of intellectual rut by focusing exclusively on this approach, neglecting or even ignoring other possible explanations.
Unfortunately, the commitment to the study of abnormal accumulations of beta-amyloid has not led to the creation of an effective drug or therapy. The need for a new non-standard way of thinking about Alzheimer's disease is becoming a top priority in brain science.
The laboratory at the University of Toronto's Krembil Brain Institute is developing a new theory of Alzheimer's disease. Based on the research of the last 30 years, scientists claim that Alzheimer's disease is mainly a disorder of the immune system in the brain.
The immune system present in each organ is a collection of cells and chemical compounds that help repair damage and protect against foreign agents. When a person stumbles and falls, the immune system helps repair damaged tissue. When someone becomes infected with a viral or bacterial infection, the immune system helps in the fight against these microbial invaders.
The same processes occur in the brain. When a head injury occurs, the brain's immune system kicks in to help with recovery. When bacteria are present in the brain, the immune system fights them back.
Alzheimer's disease as an autoimmune disease
The authors call beta-amyloid not an abnormally produced protein, but rather a normal component of the brain's immune system. According to the new theory, he should be present there. When a brain injury occurs or when bacteria are present in the brain, beta-amyloid is a key factor in the complex immune response of the brain. And that's where the problem begins.
Due to the striking similarity between lipid molecules contained in both bacterial membranes and brain cell membranes, beta-amyloid cannot distinguish invading bacteria from host brain cells and mistakenly attacks the very brain cells it is supposed to protect.
This leads to a chronic progressive loss of brain cell functions, which is pumped by dementia – and all because the body's immune system cannot distinguish bacteria from brain cells.
If we consider Alzheimer's disease as an incorrectly directed attack of the brain's immune system on the organ it is supposed to protect, then this is an autoimmune disease. There are many types of autoimmune diseases in which autoantibodies play a crucial role in the development of the disease and in which steroid hormone therapy can be effective. But these treatments won't work against Alzheimer's disease. The brain is a very special and distinctive organ, recognized as the most complex biological structure in the universe.
Although drugs traditionally used to treat autoimmune diseases may not work against Alzheimer's disease, targeting other immune-regulating pathways in the brain will lead to new and effective treatments for this disease.
Other theories of the disease
In addition to this autoimmune hypothesis of the origin of Alzheimer's disease, other new and diverse theories are being developed. For example, some scientists believe that Alzheimer's disease is a disease of the mitochondria. These are energy factories in every brain cell that convert oxygen from the air we breathe and glucose from the food we eat into the energy needed for memory and thinking. Others argue that Alzheimer's disease is the outcome of neuroinfection, and oral bacteria are often suspected as the culprits. Still others suggest that the disease may occur due to a violation of the balance of zinc, copper or iron ions in the brain.
Alzheimer's disease is a public health problem in need of innovative ideas and fresh thoughts. A better understanding of Alzheimer's disease, its causes and what can be done to treat and help people and families who live with it is necessary for the well-being of people and families living with dementia and to alleviate the socio-economic impact on an already strained healthcare system.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Conversation: Alzheimer's might not be primarily a brain disease. A new theory suggests it’s an autoimmune condition.