Special cells that wrap around the blood vessels in the brain that are abnormal leads to neuron deterioration and can possibly affect the development of Alzheimer’s disease, according to a USC-led study. These pericytes surrounding the blood vessels are called the gatekeeper cells. They dilate and contract to control the blood flow to active parts of the brain.
This pericyte degeneration might be ground zero for neurodegenerative disorders like Alzheimer’s, and possibly others. Senior author of the study and director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC, Berislav Zlokovic, says that a glitch with the gatekeeper cells that surround capillaries may restrict blood and oxygen supply to active areas of the brain that will gradually cause neuron loss that might have important implications for Alzheimer’s disease.
The study was published in Nature Neuroscience and was the first study to use a pericyte-deficient mouse model to test how the blood flow is regulated in the brain. Identifying if pericytes could be an important new therapeutic target for treating neuron deterioration was the goal of the research. The risk of cognitive impairment in many types of dementia, including Alzheimer’s disease, is increased with vascular problems. The pericytes play an important part in keeping our brains healthy.
The brain is suffocated with pericyte dysfunction that leads to metabolic stress and accelerated euronal damage with neuron loss, according to the conclusions of Zlokovic who is the holder of the Mary Hayley and Selim Zilkha Chair in Alzheimer’s disease Research.
The hind limb of young mice deficient in gatekeeper cells were stimulated, and then they monitored the global and individual responses of brain capillaries. Response of the global cerebral blood flow to an electric stimulus was reduced by about 30% compared to the normal mice, causing a weakened system. The capillaries of pericyte-deficient mice took 6.5 seconds longer to dilate than the control group where slower capillary widening and a slower flow of red blood cells carrying oxygen through capillaries meant it took longer for the brain to get its fuel.
The function of blood vessel gatekeeper cells is to ensure adequate oxygen and energy supply to brain cells. Before the study, they knew that patients with Alzheimer’s disease, ALS and other neurodegenerative disorders experienced changes to the blood flow and oxygen being supplied to the brain and that pericytes died. The new bit of information is that the loss of these gatekeeper cells leads to impaired blood flow and insufficient oxygen delivery to the brain. Now they need to know what kills pericytes in Alzheimer’s disease.
The National Institutes of Health, the National Natural Science Foundation of China and the American Heart Association supported this research. They are already working to further this line of research, scanning the brains of people who are genetically at risk for Alzheimer’s as well as collecting cerebral spinal fluid and blood for analysis of vascular damage, including injury to pericytes.
Dr Fredda Branyon