The Alzheimer’s Association reports that, by 2050, the number of people aged 65 and older with Alzheimer’s disease is projected to reach 12.7 million. As the number of patients continues to grow, the search for effective treatments becomes more urgent. But to develop effective treatments, doctors must further understand what causes Alzheimer’s disease. Recently, researchers asked: Could this devastating illness be traced back to the cells that line the body’s smallest blood vessels? According to a new study published in Molecular Therapy, the answer could be yes. Read on to find out more about the research, which involved the popular Morris Water Maze Test.
What Is the Morris Water Maze Test?
Developed by Richard Morris at the University of St. Andrews in Scotland, the Morris Water Maze Test is one of the most widely used tests in behavioral neuroscience. Researchers conducting the test begin by placing animal models – typically rats or mice – in a large circular pool of water. The animal subjects must then escape using a hidden platform. The animals must recall the platform’s location using spatial memory skills. The test’s focus on spatial memory skills makes it an effective assay of cognitive function – in animal models of Alzheimer’s disease, for example. The test was key to a new study published by a Medical University of South Carolina (MUSC) research team centering on cells known as pericytes.
How Lost Pericytes Contribute to Alzheimer’s Disease Symptoms
Pericytes – not to be confused with parasites – are specialty vascular cells that line the walls of capillaries, the tiny blood vessels throughout the body. Pericytes located in the brain serve a number of functions. First, they ensure that the brain’s energy and waste-elimination demands are met. They also help to remove amyloid-beta, the brain protein buildup often seen in Alzheimer’s disease. As vascular cells, pericytes are key to understanding Alzheimer’s disease and other dementias. After all, individuals with vascular issues – problems with their blood vessels, for example – are proven to be at increased risk of developing dementia.
Assessing Pericytes in Alzheimer’s Disease Brains
We now know that, when pericytes are lost, mental function can decline soon after. This is because pericytes serve as a sort of clean-up crew, clearing excess immune cells and impurities from the vascular system that feed the brain. Without that clean-up crew, impurities can leak into the brain and cause inflammation and cell death. This was confirmed by the MUSC team after a thorough analysis of several brains of people who had died of Alzheimer’s disease. Per the study, the MUSC team found that the affected brains had 34 percent fewer pericytes than healthy brains. The pericytes were specifically low in the hippocampus, an important part of the brain associated with learning and memory.
Interestingly, the remaining pericytes in Alzheimer’s disease brains showed surprisingly high levels of Fli-1, an important protein coding gene. With that, the researchers wanted to know: Could manually blocking Fli-1 improve cognitive function?
Assessing Animal Models with the Morris Water Maze Test
To evaluate the Fli-1 hypothesis, the researchers assessed the brain of a 5xFAD mouse model of Alzheimer’s disease. That brain also showed pericyte loss in the hippocampus, as well as increased Fli-1. With that in mind, the researchers chose to block Fli-1 and study the effects on this 5xFAD mouse model. Interestingly, blocking Fli-1 improved the mice’s performance on behavioral tests – including the Morris Water Maze Test. The team also found that blocking Fli-1 in the mouse model helped to prevent pericyte loss, as well as reduce amyloid-beta buildup.
The MUSC team’s findings could be crucial in the hunt for effective Alzheimer’s disease treatments. “What’s exciting is that this could be a new way to think about treating Alzheimer’s disease, which has never been thought of before,” said researcher Perry Halushka. “This research opens up a whole new area for potential targets, not just Fli-1 but the pericyte itself.”
QPS Neuropharmacology is a division of QPS, a GLP/GCP-compliant contract research organization (CRO) delivering the highest grade of discovery, preclinical, and clinical drug development services since 1995. QPS Neuropharmacology focuses on preclinical studies related to central nervous system (CNS) diseases, rare diseases, and mental disorders. With highly predictive disease models available on site and unparalleled preclinical experience, QPS Neuropharmacology can handle most CNS drug development needs for biopharmaceutical companies of all sizes. To study Alzheimer’s disease, QPS Neuropharmacology offers several in vivo models, including the 5xFAD mouse model, corresponding learning and memory behavioral tests as well as ex vivo analysis tools. For more information about QPS visit www.qps.com, and for more information about QPS Neuropharmacology, visit www.qpsneuro.com.