Anti-APOE antibodies effectively remove amyloid deposition

The amyloid deposition in the brain is one of the signature features of Alzheimer's patients, so there are a number of studies designed to remove these amyloid deposits, one of which is the use of monoclonal antibodies that bind to amyloid. They stimulate small glial cells in the brain to remove amyloid deposits. However, this treatment is usually accompanied by an adverse reaction called ARIA. ARIA's full name is amyloid protein-related imaging abnormalities, which may be a sign of cerebral edema (ARIA-E) or micro-bleeding (ARIA-H). This adverse reaction limits the use of anti-amyloid antibodies to some extent.A team of researchers at the University of Washington and Denali Therapeutics recently found that a monoclonal antibody targeting APOE did not increase the risk of brain bleeding while effectively removing amyloid deposits from brain tissue and blood vessels in animal models. Researchers say it could be a safer potential treatment for Alzheimer's disease. The study was published in the latest issue of TranslationAl Medicine.ARIA may be caused by an overly inflammatory response, so the researchers speculate that if monoclonal antibodies can target a small portion of amyloid deposition, it may be able to prevent ARIA production while removing protein deposition. For the study, scientists used a monoclonal antibody that targeted a specific form of APOE protein. APOE's allied gene is the largest genetic risk factor for late-onset Alzheimer's disease. APOE protein also plays an important role in the formation of amyloid protein deposition.The monoclonal antibody, called HAE-4, targets APOE proteins that are present in small amounts in amyloid deposition. In mouse animal models of Alzheimer's disease and cerebral amyloid vascular disease (CAA, a disease caused by amyloid protein deposition in blood vessels), HAE-4 antibodies were able to effectively remove amyloid deposition in brain tissue and blood vessels compared to anti-amyloid antibodies. At the same time, there is no increased risk of blood vessel microbleeding. The researchers also found that HAE-4 antibodies, like anti-amyloid proteins, initially triggered an immune response to amyloid deposition. But inflammation in mice treated with HAE-4 antibodies was eliminated within two months, while inflammation inspired by anti-amyloid antibodies persisted.“ For decades, researchers have been looking for treatments to remove amyloid from the brain, and recently we finally had some promising treatments in progress, but we've found complications like ARIA. Study senior author Dr David Holtzman, head of the Department of Neurology at the University of Washington, said: "We have opened up a new approach by targeting APOE. It appears to be able to effectively remove amyloid protein from brain tissue and blood vessels while avoiding this potentially dangerous side effect. Note : This article is intended to introduce medical and health research, not treatment options recommended. For guidance on treatment options, visit a regular hospital. (Pharmaceutical Mingkangde):Xiong et al., (2021). APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function. Science Translational Medicine, DOI: 10.1126/scitranslmed.abd7522.[2] Protein linked to Alzheimer's, strokes cleared from brain blood vessels. Retrieved February 18, 2021, from