In Alzheimer's patients, the blood supply is disrupted and therefore the energy supply to the brain cells decreases. One of the reasons for the decrease in energy supply may be explained by the collapse of the blood-brain barrier
By Kira Shaw, Neuroscience Postdoctoral Fellow, University of Sussex, UK and Orla Bonnar, PhD Candidate, also from Sussex University
It is known that Alzheimer's disease, the most common form of dementia, is involved in the accumulation of sticky proteins (amyloids) in the brain. But we still do not know what the primary cause of the disease is. Given that someone, somewhere unknown is diagnosed with dementia every three seconds, there is a mad race to discover the cause of the disease so that an effective treatment can be developed for it.
Scientists now know that changes in the blood flow in the brain occur before the appearance of the amyloid nodules and this has led to an interesting theory for the origin of the disease - the vascular theory.
When the brain cells become active, they need energy in the form of glucose and oxygen that arrive through the transfer of increased blood supply to this area of the brain (through the blood-brain barrier), but in Alzheimer's patients the blood supply is disrupted and therefore the energy supply to the brain cells decreases. One of the reasons for the decrease in energy supply may be explained by the collapse of the blood-brain barrier.
The capillaries in the brain are combined with tightly packed anotel cells that form a semi-permeable barrier. They allow oxygen, glucose and other necessary substances to pass through the barrier but prevent larger molecules from crossing it and entering the brain. Researchers have shown that in Alzheimer's patients the reliability of this barrier is less due to cracks that form in the otherwise tight structure of the endothelial cells. This leads to the accumulation of harmful molecules in the brain, which in turn cause swelling in the brain and reduced blood flow to it.
The lack of oxygen in the blood, a condition known as hypoxia, reduces the ability of neurons to generate an electrical current and changes the chemistry of the brain. This causes swelling and lesions in the brain and more importantly - helps to create the beta-amyloid clumps and the tau tangles - the features most associated with Alzheimer's. Therefore, the development of these blood vessels in the brain may start a vicious cycle, which will eventually lead to mass cell death.
The role of the APOE gene
Another clue that Alzheimer's disease may have been caused by impaired blood flow to the brain comes from genetics.
The gene associated with a high risk of developing Alzheimer's later in life is called APOE. Each of us carries two copies of the kindergarten, one from each parent. The APOE exists in three versions (three alleles) called e2, e3 and e4. People with two copies of the e4 allele ("APOE4") have an increased risk of developing Alzheimer's 3-5 times higher than the general population.
Researchers at Johns Hopkins University showed that people with the APOE4 gene suffered from reduced blood flow, without any symptoms of Alzheimer's. In a separate study done on genetically engineered mice into which the APOE gene was inserted, it was shown that APOE4 causes capillary damage before evidence of brain cell deterioration is seen. These findings support the idea that blood flow disruption may be one of the early changes in the body leading to Alzheimer's.
The vascular theory may explain why people who have had high blood pressure or had a stroke are more likely to develop the disease. High blood pressure causes blood clots to form in the arteries leading to the brain, which reduces blood flow and oxygenation. A stroke may be caused by these blood clots because the blood supply to part of the brain is suddenly stopped. Both symptoms cause a decrease in the energy supply to the brain, which causes significant damage to the brain cells.
We need another goal
There is no cure for Alzheimer's disease, but only drugs to treat some of the symptoms. The new treatments being researched today tend to focus on removing the accumulated substances, which may or may not restore function. But perhaps a better target for drug developers would be to treat the changes that occur in the blood vessels before the brain cells are affected.
In a 2012 study, published in the journal Nature researchers at the University of Rochester gave a drug that suppresses the immune system - cyclosporine to mice with a human APOE4 genome. They showed that following the treatment the early damage to the capillaries and the blood-brain barrier is healed. Obviously, genetically modified mice are not the same as humans, but the findings lead to further support for the vascular theory.
And more than shedding light on possibilities for new drugs, the vascular theory also emphasizes the importance of maintaining good heart and blood vessel health. Physical activity increases the heart rate and blood flow to the brain, which increases the oxygen level and improves the overall health of the brain cells. As the saying goes, an ounce of prevention is worth a pound of cure.
Full Disclosure
Bonnar receives funding from the Alzheimer's Association, Shaw does not work for, advise, hold stock in, or receive funding from any company or organization that may benefit from this article, and has no affiliation other than the academic appointment.
To the article on The Conversation website - the British edition
More of the topic in Hayadan:
- Researchers from Tel Aviv University found that the RGS2 gene appears at significantly reduced levels in the blood of Alzheimer's patients
- Researchers at Tel Aviv University have developed a new approach to treating Alzheimer's, which has been proven effective in laboratory animals - The researchers focused on the gene known as ApoE, whose defective form (ApoE4) appears in about 60% of Alzheimer's patients
- Researchers at the Weizmann Institute discovered how to break down clumps of proteins that are not folded correctly, in Alzheimer's and Parkinson's patients?
