Women are at a higher risk than men of developing Alzheimer\u2019s disease. So are people who carry a particular variant of a gene that everyone has, called APOE.<\/p>\n
With a $300,000 research grant from the Alzheimer\u2019s Association, a team of scientists, led by psychology and neuroscience distinguished professor Karyn Frick will dive into why women with two variants of the APOE gene are more protected from Alzheimer\u2019s when they take estrogen therapy, while those with a third variant aren\u2019t.<\/p>\n
Almost two in three Americans with Alzheimer\u2019s are women, according to the Alzheimer\u2019s Association 2022 Alzheimer\u2019s Disease Facts and Figures. The hormone estrogen protects the brain cells that create and store memories, but estrogen levels decline during menopause, leaving women\u2019s brains more vulnerable to the disease.<\/p>\n
Estrogen therapy reduces the odds for some women. Previous research has shown that one of the APOE gene\u2019s three variants, dubbed E4, shows resistance to estrogen\u2019s brain benefits. The other variants, E2 and E3, are not resistant to estrogen therapy.<\/p>\n
The researchers\u2019 aim is to find the most effective estrogen compound for each APOE variant to move into human clinical trials.<\/p>\n
\u201cWe are excited to support this very important work being done by Dr. Frick and her colleagues,\u201d said David Grams, executive director of the Alzheimer\u2019s Association Wisconsin Chapter. \u201cWe are committed to investing in promising and innovative research and we\u2019re proud that Wisconsin is home to scientists who are dedicated to helping us find a cure for this devastating disease.\u201d<\/p>\n
\u201cAll people carry two APOE variants in different combinations,\u201d Frick said, \u201cSo risk would be different depending on whether a woman carries the E3\/3, E3\/4 or E4\/4 variants.\u201d<\/p>\n
Using an Alzheimer\u2019s mouse model developed by another team member, Mary Jo LaDu of the University of Illinois at Chicago, the researchers will compare oral treatment of a potent estrogen called estradiol along with two novel estrogen compounds on mice that have the APOE variants E3\/4 and E4\/4.<\/p>\n
These treatments target another part needed to solve the Alzheimer\u2019s puzzle in women \u2013 estrogen receptors. In order to influence cell function estrogens must enter the cells and bind to these receptors.<\/p>\n
APOE is a gene that\u2019s responsible for transporting cholesterol and other types of fats \u2013 or lipids \u2013 to cells where they can be used or disposed of. Exactly how it\u2019s involved in women\u2019s risk of Alzheimer\u2019s is not fully understood, but the Frick team is working on a hypothesis.<\/p>\n
\u201cWe think the reason is that E4 doesn\u2019t do as good a job of clearing lipids and carrying them into cells as E3 and E2 do,\u201d Frick said.<\/p>\n
That\u2019s important because both the hormone estrogen and amyloid, a toxic protein that builds up in the Alzheimer\u2019s brain, are lipids, she said.<\/p>\n
Many women are reluctant to take hormone therapy, whether it be for memory protection or to ease bothersome menopausal symptoms, because estrogen therapy can increase the risk of breast or uterine cancer and cardiovascular disease for some people. With colleagues from Concordia University Wisconsin and Marquette University, Frick formed the startup Estrigenix Therapeutics, Inc., with the goal of developing drug compounds that provide the benefits of estrogens without harmful side effects.<\/p>\n
Her research team will be testing one of Estrigenix\u2019s compounds with this funding, which may provide a new avenue for developing treatments that reduce Alzheimer\u2019s risk in women of multiple APOE variants.<\/p>\n
The Alzheimer\u2019s Association is the largest nonprofit funder of Alzheimer\u2019s research in the world, investing over $310 million in more than 950 projects in 48 countries.<\/p>\n
By University Relations<\/small><\/strong><\/em><\/p>\n","protected":false},"excerpt":{"rendered":" Women are at a higher risk than men of developing Alzheimer\u2019s disease. So are people who carry a particular variant of a gene that everyone has, called APOE. With a $300,000 research grant from the Alzheimer\u2019s Association, a team of …<\/p>\n","protected":false},"author":32664,"featured_media":19710,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","uwm_wg_additional_authors":[]},"categories":[1734],"tags":[1860],"class_list":["post-19694","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-in-focus-2022","tag-october"],"yoast_head":"\n