People with harmful forms of the APOE<\/em> gene have up to 12 times the risk of developing Alzheimer\u2019s disease<\/strong> compared with those who have other variations of the gene.<\/p>\n Many researchers believe that the memory loss and cognitive problems of Alzheimer\u2019s result from the buildup over many years of brain amyloid plaques. The plaques are made mostly of a sticky substance called amyloid beta.<\/p>\n For years, researchers have thought that the APOE<\/em> gene increases Alzheimer\u2019s risk by producing a protein that binds to amyloid beta<\/strong>. Scientists thought that this bond could make it easier for plaques to form.<\/p>\n But in a new study now available online in the Proceedings of the National Academy of Sciences<\/em>, Washington University researchers show that APOE and amyloid beta don\u2019t bind together in cerebrospinal fluid and in fluids present outside cells grown in dishes. This means they are unlikely to bind together in the fluids circulating in the brain<\/strong>. The cerebrospinal fluid was taken from people who were cognitively normal but have forms of APOE<\/em> that increase the risk of Alzheimer\u2019s.<\/p>\n \u201cThis is the first time we\u2019ve looked at naturally produced APOE and amyloid beta to see if and how much they bind together, and we found that they have very little interaction in the fluids bathing the brain,\u201d said David M. Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of neurology. \u201cThis suggests that we may need to rethink any therapeutic strategies that target APOE to slow amyloid plaque accumulation and Alzheimer\u2019s.<\/strong>\u201d<\/p>\n According to Holtzman, leading Alzheimer\u2019s researchers recently agreed that targeting APOE is a promising approach both for gaining a better understanding of and improving treatments for Alzheimer\u2019s. But to do that, scientists must first fully understand how the harmful forms of APOE<\/em> increase risk of the disease.<\/p>\n \u201cAPOE<\/em> is a major player in Alzheimer\u2019s, there\u2019s no question about that,\u201d said Philip Verghese, PhD, a postdoctoral research associate. \u201cWe did some additional studies in mice and cell cultures that suggested the APOE protein may be blocking a pathway that normally helps degrade amyloid beta.\u201d<\/p>\n APOE<\/em> is involved in the metabolism of fats, cholesterol and vitamins throughout the body. Scientists have identified three different forms of the gene that each make a slightly different version of the protein.<\/p>\n One version, APOE 2<\/em>, produces a protein that significantly reduces Alzheimer\u2019s risk. Another, APOE 4<\/em>, increases risk<\/strong>. Each person has two copies of the gene, and if both copies are APOE 4<\/em>, the chance of developing Alzheimer\u2019s rises dramatically.<\/p>\n \u201cAbout 60 percent of the patients we see in the Alzheimer\u2019s clinics have at least one copy of APOE 4<\/em>,\u201d Holtzman said. \u201cIn contrast, only about 25 percent of cognitively normal 70-year-olds have a copy of APOE 4<\/em>.\u201d<\/p>\n Verghese tested cerebrospinal fluid samples from people who had either two copies of APOE 4<\/em> or two copies of APOE 3<\/em>, another form of the gene that is not associated with\u00a0 increased Alzheimer\u2019s risk.<\/p>\n \u201cWe also found that APOE 2, the protective form of the protein, doesn\u2019t bind to amyloid beta in body fluids<\/strong>,\u201d Verghese said.<\/p>\n In follow-up studies, Verghese showed that APOE and amyloid beta \u201ccompete\u201d to bind to a receptor on support cells in the brain known as astrocytes.<\/p>\n \u201cStudies by other researchers have shown that astrocytes can degrade amyloid beta,\u201d Verghese said. \u201cThe receptor we identified may be important for getting amyloid beta into the astrocyte so it can be broken down<\/strong>. It\u2019s possible that when the harmful forms of APOE bind to the receptor, this reduces the opportunities for amyloid to be degraded.\u201d<\/p>\n The researchers are planning follow-up studies of the effects of APOE-blocking treatments in mice.<\/p><\/blockquote>\n","protected":false},"excerpt":{"rendered":" From the Washington University School of Medicine in St. Louis press release by Michael C. Purdy via HealthCanal: Scientists\u2019 picture of how a gene strongly linked to Alzheimer\u2019s disease harms… Read more »<\/a><\/p>\n","protected":false},"author":5,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[321,6],"tags":[195,42,18,194,234],"_links":{"self":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/12785"}],"collection":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/comments?post=12785"}],"version-history":[{"count":5,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/12785\/revisions"}],"predecessor-version":[{"id":13499,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/posts\/12785\/revisions\/13499"}],"wp:attachment":[{"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/media?parent=12785"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/categories?post=12785"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/therapytoronto.ca\/news\/wp-json\/wp\/v2\/tags?post=12785"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}![\"senior_medication\"](\"http:\/\/therapytoronto.ca\/news\/wp-content\/uploads\/2012\/12\/senior_medication1.jpg\")
Scientists\u2019 picture of how a gene strongly linked to Alzheimer\u2019s disease harms the brain may have to be revised<\/strong>, researchers at Washington University School of Medicine in St. Louis have found.<\/p>\n