{"id":11,"date":"2017-12-22T22:05:52","date_gmt":"2017-12-22T22:05:52","guid":{"rendered":"http:\/\/gero.usc.edu\/labs\/pikelab\/?page_id=11"},"modified":"2023-08-18T23:03:25","modified_gmt":"2023-08-18T23:03:25","slug":"research","status":"publish","type":"page","link":"https:\/\/gero.usc.edu\/labs\/pikelab\/research\/","title":{"rendered":"Research"},"content":{"rendered":"<div class=\"wpb-content-wrapper\"><p>[vc_row][vc_column][vc_single_image image=&#8221;20&#8243; img_size=&#8221;1600X400&#8243; alignment=&#8221;center&#8221;][vc_empty_space height=&#8221;10&#8243;][vc_column_text]Ongoing research projects in the Pike Lab are using a range of rodent models, cell culture paradigms and analyses of human tissues both to investigate underlying factors in Alzheimer\u2019s pathogenesis and to develop translatable approaches to prevent and treat the disease. Current investigations, outlined below, emphasize the interactive risks of obesity and depletion of sex steroid hormones as well as pursue two promising, novel therapeutic strategies.[\/vc_column_text][\/vc_column][\/vc_row][vc_row el_id=&#8221;sex-differences&#8221;][vc_column][vc_custom_heading text=&#8221;Sex differences in AD risk associated with APOE4&#8243; font_container=&#8221;tag:h3|text_align:left&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text]APOE4, the primary genetic risk factor for Alzheimer\u2019s disease (AD), causes a greater lifetime risk and an increased rate of cognitive decline in women compared to men. The reasons for this sex-based link remain unknown. Our collaborative team is investigating the novel hypothesis that normal developmental processes that underlie sexual differentiation yield a female brain that is inherently more vulnerable to the effects of APOE4. We are examining this hypothesis using both human twin populations and transgenic mice that harbor human APOE alleles and AD transgenes. The results of this research will provide essential information to address the critical need for treatment options for women at high risk for AD from APOE4.[\/vc_column_text][\/vc_column][\/vc_row][vc_row el_id=&#8221;menopause&#8221;][vc_column][vc_custom_heading text=&#8221;Protective diets as prevention and treatment strategies against APOE4 and Alzheimer\u2019s disease&#8221; font_container=&#8221;tag:h3|text_align:left&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text]The E4 allele of apolipoprotein E (<i>APOE4<\/i>) is associated with accelerated aging and mortality as well increased vulnerability to Alzheimer\u2019s disease (AD). Although the causal links between\u00a0<i>APOE4<\/i>, aging, and AD risk remain to be fully defined, candidate mechanisms include regulation of energy metabolism and systemic and neural inflammatory tone. Recent findings from our collaborator Valter Longo demonstrate that nutritional approaches, including fasting mimicking diet (FMD), exhibit anti-aging and protective properties across several age-related conditions. Indeed, pathways identified to be beneficially regulated by FMD and related nutritional interventions overlap with pathways thought to underlie relationships among\u00a0<i>APOE4<\/i>, aging, and AD. In an ongoing series of studies, we investigate the hypothesis that FMD and related dietary interventions will protect against\u00a0<i>APOE4\u00a0<\/i>phenotypes that drive age-related cognitive impairment and AD pathogenesis.[\/vc_column_text][\/vc_column][\/vc_row][vc_row el_id=&#8221;interactions&#8221;][vc_column][vc_custom_heading text=&#8221;Longevity-promoting compounds as protectants against APOE4 and Alzheimer\u2019s disease&#8221; font_container=&#8221;tag:h3|text_align:left&#8221; use_theme_fonts=&#8221;yes&#8221;][vc_column_text]Increasing age is the most significant risk factor for developing Alzheimer\u2019s disease (AD).\u00a0<i>APOE\u00a0<\/i>is the most common genetic AD risk factor: AD risk is reduced by the\u00a0<i>APOE2\u00a0<\/i>allele and increased by the\u00a0<i>APOE4\u00a0<\/i>allele. Interestingly,\u00a0<i>APOE\u00a0<\/i>genotype is associated with\u00a0 longevity, whereby\u00a0<i>APOE2\u00a0<\/i>is linked with increased and\u00a0<i>APOE4\u00a0<\/i>decreased longevity. This same pattern is observed with AD, in which risk follows an\u00a0<i>APOE2 \u00a0<\/i>&lt;\u00a0<i>APOE3 \u00a0<\/i>&lt;\u00a0<i>APOE4\u00a0<\/i>pattern. An intriguing possibility is that the relationships between AD risk and\u00a0<i>APOE\u00a0<\/i>genotypes are mediated in part by regulation of systemic aging. Thus, age-related phenotypes associated with\u00a0<i>APOE4\u00a0<\/i>are predicted to contribute to its increased AD risk. Indeed, aging and\u00a0<i>APOE4\u00a0<\/i>share several phenotypes that are linked with AD pathogenesis, including systemic and neural metabolic dysfunction and inflammation. We are actively pursuing several studies investigating the hypothesis that the longevity-promoting interventions will preferentially protect against\u00a0<i>APOE4\u00a0<\/i>phenotypes that drive AD pathogenesis. These studies have potentially profound impact in that they suggest the possibility that senescent, AD-related phenotypes associated with\u00a0<i>APOE4\u00a0<\/i>may be prevented by longevity-promoting treatments in middle age.[\/vc_column_text][\/vc_column][\/vc_row]<\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>[vc_row][vc_column][vc_single_image image=&#8221;20&#8243; img_size=&#8221;1600X400&#8243; alignment=&#8221;center&#8221;][vc_empty_space height=&#8221;10&#8243;][vc_column_text]Ongoing research projects in the Pike Lab are using a range of rodent models, cell culture paradigms and analyses of human tissues both to investigate underlying factors in Alzheimer\u2019s pathogenesis and to develop translatable approaches to prevent and treat the disease. Current investigations, outlined below, emphasize the interactive risks of obesity [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-full.php","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-11","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Research - The Pike Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/gero.usc.edu\/labs\/pikelab\/research\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Research - The Pike Lab\" \/>\n<meta property=\"og:description\" content=\"[vc_row][vc_column][vc_single_image image=&#8221;20&#8243; img_size=&#8221;1600X400&#8243; alignment=&#8221;center&#8221;][vc_empty_space height=&#8221;10&#8243;][vc_column_text]Ongoing research projects in the Pike Lab are using a range of rodent models, cell culture paradigms and analyses of human tissues both to investigate underlying factors in Alzheimer\u2019s pathogenesis and to develop translatable approaches to prevent and treat the disease. Current investigations, outlined below, emphasize the interactive risks of obesity [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/gero.usc.edu\/labs\/pikelab\/research\/\" \/>\n<meta property=\"og:site_name\" content=\"The Pike Lab\" \/>\n<meta property=\"article:modified_time\" content=\"2023-08-18T23:03:25+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/research\\\/\",\"url\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/research\\\/\",\"name\":\"Research - The Pike Lab\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/#website\"},\"datePublished\":\"2017-12-22T22:05:52+00:00\",\"dateModified\":\"2023-08-18T23:03:25+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/research\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/research\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/research\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/#website\",\"url\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/\",\"name\":\"The Pike Lab\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/gero.usc.edu\\\/labs\\\/pikelab\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Research - The Pike Lab","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/gero.usc.edu\/labs\/pikelab\/research\/","og_locale":"en_US","og_type":"article","og_title":"Research - The Pike Lab","og_description":"[vc_row][vc_column][vc_single_image image=&#8221;20&#8243; img_size=&#8221;1600X400&#8243; alignment=&#8221;center&#8221;][vc_empty_space height=&#8221;10&#8243;][vc_column_text]Ongoing research projects in the Pike Lab are using a range of rodent models, cell culture paradigms and analyses of human tissues both to investigate underlying factors in Alzheimer\u2019s pathogenesis and to develop translatable approaches to prevent and treat the disease. 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