Blocking overactive receptor in Alzheimer鈥檚 recovers memory loss and more
A new study shows that memory pathology in older mice with Alzheimer鈥檚 disease can be reversed with treatment. The study by researchers from the Montreal Neurological Institute and Hospital - The Neuro, at 平特五不中 and at Universit茅 de Montr茅al found that blocking the activity of a specific receptor in the brain of mice with advanced Alzheimer鈥檚 disease (AD) recovers memory and cerebrovascular function. The results, published in the Journal of Neuroinflammation in May, also suggest an underlying mechanism of AD as a potential target for new therapies.
鈥淭he exciting and important aspect of this study is that even animals with advanced pathology can be rescued with this molecule鈥� says Dr. Edith Hamel, neuroscientist at The Neuro and lead investigator on the paper in collaboration with Dr R茅jean Couture at the Department of Physiology at Universit茅 de Montr茅al. 鈥淲e have rarely seen this type of reversal of AD symptoms before in our mouse model at this advanced age 鈥� when mice have been developing AD for one year.鈥�
The researchers found an increased level of a receptor known as bradykinin B1 receptor (B1R) in the brain of mice with AD, a receptor involved in inflammation. 聽鈥淏y administering a molecule that selectively blocks the action of this receptor, we observed important improvements in both cognitive and cerebrovascular function,鈥� says Dr. Baptiste Lacoste, research fellow who conducted the study at The Neuro and now pursuing his training at Harvard Medical School in Boston. 鈥淎lzheimer鈥檚 disease destroys nerve cells and also compromises the function of blood vessels in the brain. Not only were there improvements in learning and memory, but also marked recovery in blood flow and vascular reactivity, i.e. the ability of cerebral vessels to dilate or constrict when necessary.鈥� Proper functioning of blood vessels in the brain is vital to providing nutrients and oxygen to nerve cells, and vascular diseases represent important risk factors for developing AD at an advanced age.
鈥淎nother interesting result that has not been seen before in our mouse model is a reduction by over 50% of toxic amyloid-beta peptide,鈥� adds Dr. Hamel. 聽鈥淚n Alzheimer鈥檚 disease, protein fragments called amyloid-beta have a deleterious effect on the blood and nervous systems. Normally, these protein fragments are broken down and removed. In Alzheimer鈥檚 disease, the protein fragments clump together 鈥� a factor believed to contribute to neuronal and vascular dysfunction. We are not sure if these decreases contribute to the functional recovery, but we hope that our findings will aid in clarifying this issue and identifying new targets for therapeutic approaches.鈥�
The results show that an increase in B1R is associated with amyloid-beta plaques in Alzheimer鈥檚 disease mice with impaired memory, and that chronic blockade of B1R significantly improves learning, memory, cerebrovascular function, and several other pathological AD hallmarks in mice with a fully developed pathology. Together, these findings confirm a role of B1R in AD pathogenesis and the role of neuroinflammation as an underlying mechanism in AD. The next step would be to further investigate potential blockers of the bradykinin B1R as a potential treatment for AD in humans.
This study was funded by the Canadian Institutes of Health Research and a postdoctoral fellowship award from the Alzheimer Society of Canada.
Link to the study: 聽
The Neuro
The Montreal Neurological Institute and Hospital 鈥� The Neuro, is a unique academic medical centre dedicated to neuroscience. Founded in 1934 by the renowned Dr. Wilder Penfield, the Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. The Neuro is a research and teaching institute of 平特五不中 and forms the basis for the Neuroscience Mission of the 平特五不中 Health Centre.聽 Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. For more information, visit theneuro.com