{"id":3351,"date":"2026-03-11T12:53:25","date_gmt":"2026-03-11T16:53:25","guid":{"rendered":"https:\/\/www.centre-stopad.com\/?p=3351"},"modified":"2026-03-13T14:09:24","modified_gmt":"2026-03-13T18:09:24","slug":"sex-differences-in-p-tau217-tau-aggregation-and-cognitive-decline-coughlan-et-al-2026","status":"publish","type":"post","link":"https:\/\/www.centre-stopad.com\/en\/2026\/03\/11\/sex-differences-in-p-tau217-tau-aggregation-and-cognitive-decline-coughlan-et-al-2026\/","title":{"rendered":"Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline (Coughlan et al., 2026)"},"content":{"rendered":"<div class=\"wp-block-stackable-columns stk-block-columns stk-block stk-f68af85\" data-block-id=\"f68af85\"><style>.stk-f68af85-column{--stk-columns-spacing:12px !important;--stk-column-gap:12px !important;}<\/style><div class=\"stk-row stk-inner-blocks stk-block-content stk-content-align stk-f68af85-column\">\n<div class=\"wp-block-stackable-column stk-block-column stk-column stk-block stk-0bb6bd7\" data-v=\"4\" data-block-id=\"0bb6bd7\"><style>@media screen and (min-width: 768px){.stk-0bb6bd7 {flex:var(--stk-flex-grow, 1) 1 calc(25% - var(--stk-column-gap, 0px) * 1 \/ 2 ) !important;}}<\/style><div class=\"stk-column-wrapper stk-block-column__content stk-container stk-0bb6bd7-container stk--no-background stk--no-padding\"><div class=\"stk-block-content stk-inner-blocks stk-0bb6bd7-inner-blocks\">\n<div class=\"wp-block-stackable-image stk-block-image stk-block stk-3a7774a\" data-block-id=\"3a7774a\"><figure><span class=\"stk-img-wrapper stk-image--shape-stretch\"><img loading=\"lazy\" decoding=\"async\" class=\"stk-img wp-image-3430\" src=\"https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png\" width=\"300\" height=\"300\" srcset=\"https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png 300w, https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2-150x150.png 150w, https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2-12x12.png 12w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/span><\/figure><\/div>\n\n\n\n<div class=\"wp-block-stackable-text stk-block-text stk-block stk-fc0d2be\" data-block-id=\"fc0d2be\"><style>.stk-fc0d2be .stk-block-text__text{font-size:12px !important;}@media screen and (max-width: 1023px){.stk-fc0d2be .stk-block-text__text{font-size:12px !important;}}<\/style><p class=\"stk-block-text__text\"><span style=\"color: #abb8c3;\" class=\"stk-highlight\"><strong>Citation : <\/strong><br>Coughlan, G. T., Ourry, V., Townsend, D., Klinger, H., Brown, J. A., Cuppels, M., Betthauser, T., Langhough, R., Cody, K., Seto, M., Birkenbihl, C., Li, A., Farrell, M., Thibault, E., Kivis\u00e4kk Webb, P., Arnold, S., Rissman, R. A., Properzi, M., Schultz, A., Johnson, K., \u2026 A4 Study Team, the Alzheimer\u2019s Disease Neuroimaging Initiative, and the PREVENT-AD Research Group (2026). Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline.&nbsp;<em>JAMA neurology<\/em>, e255670. Advance online publication. https:\/\/doi.org\/10.1001\/jamaneurol.2025.5670<\/span><\/p><\/div>\n\n\n\n<div class=\"wp-block-stackable-text stk-block-text stk-block stk-0055278\" data-block-id=\"0055278\"><style>.stk-0055278 .stk-block-text__text{font-size:12px !important;}@media screen and (max-width: 1023px){.stk-0055278 .stk-block-text__text{font-size:12px !important;}}<\/style><p class=\"stk-block-text__text\"><span style=\"color: #0693e3;\" class=\"stk-highlight\">Full text : <\/span><a href=\"https:\/\/doi.org\/10.1001\/jamaneurol.2025.5670\" target=\"_blank\" rel=\"noreferrer noopener\">Here<\/a><\/p><\/div>\n<\/div><\/div><\/div>\n\n\n\n<div class=\"wp-block-stackable-column stk-block-column stk-column stk-block stk-36f0c6d\" data-v=\"4\" data-block-id=\"36f0c6d\"><style>@media screen and (min-width: 768px){.stk-36f0c6d {flex:var(--stk-flex-grow, 1) 1 calc(75% - var(--stk-column-gap, 0px) * 1 \/ 2 ) !important;}}<\/style><div class=\"stk-column-wrapper stk-block-column__content stk-container stk-36f0c6d-container stk--no-background stk--no-padding\"><div class=\"stk-block-content stk-inner-blocks stk-36f0c6d-inner-blocks\">\n<div class=\"wp-block-stackable-heading stk-block-heading stk-block-heading--v2 stk-block stk-4b1e40a\" id=\"a-href-https-doi-org-10-1001-jamaneurol-2025-5670-span-style-color-var-ast-global-color-0-class-stk-highlight-sex-differences-in-p-tau-217-tau-aggregation-and-cognitive-decline-span-a\" data-block-id=\"4b1e40a\"><h2 class=\"stk-block-heading__text\"><a href=\"https:\/\/doi.org\/10.1001\/jamaneurol.2025.5670\"><span style=\"color: var(--ast-global-color-0);\" class=\"stk-highlight\">Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline<\/span><\/a><\/h2><\/div>\n\n\n\n<div class=\"wp-block-stackable-text stk-block-text stk-block stk-c5ea493\" data-block-id=\"c5ea493\"><p class=\"stk-block-text__text has-text-align-justify\"><strong>Gillian T Coughlan, Valentin Ourry, Diana Townsend, Hannah Klinger, Jane A Brown, Madison Cuppels, Tobey Betthauser, Rebecca Langhough, Karly Cody, Mabel Seto, Colin Birkenbihl, Annie Li, Michelle Farrell, Emma Thibault, Pia Kivis\u00e4kk Webb, Steven Arnold, Robert A Rissman, Michael Properzi, Aaron Schultz, Keith Johnson, Oliver Langford, Michael C Donohue, Sylvia Villeneuve, Sterling C Johnson, Hyun-Sik Yang, JoAnn E Manson, Reisa Sperling, Rachel F Buckley; A4 Study Team, the Alzheimer\u2019s Disease Neuroimaging Initiative, and the PREVENT-AD Research Group<\/strong><br><br>published in <em>JAMA Neurology<\/em>, February 2026. <\/p><\/div>\n\n\n\n<div class=\"wp-block-stackable-text stk-block-text stk-block stk-b6385a4\" data-block-id=\"b6385a4\"><style>.stk-b6385a4 .stk-block-text__text{font-size:12px !important;}@media screen and (max-width: 1023px){.stk-b6385a4 .stk-block-text__text{font-size:12px !important;}}<\/style><p class=\"stk-block-text__text has-text-align-justify\"><strong>ABSTRACT<\/strong> <strong>:<\/strong><br><br><strong>Importance:&nbsp;<\/strong>Among individuals with high levels of amyloid-\u03b2 (A\u03b2), women exhibit higher insoluble tau burden and accumulation than age-matched men. It remains unclear whether this sex difference is influenced by soluble phosphorylated tau (p-tau), a biomarker that changes early in Alzheimer disease.<br><br><strong>Objective:&nbsp;<\/strong>To investigate whether sex and aggregated A\u03b2 synergistically predict plasma phosphorylated tau 217 (p-tau217) levels and whether levels of p-tau217 predict cross-sectional and longitudinal tau aggregation in a sex-specific manner (as measured by positron emission tomography [PET]).<br><br><strong>Design, setting, and participants:&nbsp;<\/strong>This longitudinal study analyzed data between September 7, 2024, and October 29, 2025, from 1 clinical trial cohort and 4 observational study cohorts including men and women without cognitive impairment who had undergone multiple assessments via tau PET (18F-flortaucipir or 18F-MK-6240) and plasma p-tau217 assay at baseline. Cognitive performance was measured with the Preclinical Alzheimer Cognitive Composite. Data on cognitive performance were available from 3 of the 5 cohorts for a mean of 4.6 years (SD, 3.1 years). Across the 5 cohorts, the mean follow-up for tau PET was 3.6 years (SD, 1.7 years).<br><br><strong>Exposures:&nbsp;<\/strong>Self-reported sex (male or female), tau PET, and p-tau217 assay.<br><br><strong>Main outcomes and measures:&nbsp;<\/strong>The primary analyses used linear and mixed-effects models to assess baseline and longitudinal sex \u00d7 p-tau217 interactions for 9 tau PET regions. The secondary analyses assessed sex \u00d7 p-tau217 interactions for cognitive change using the Preclinical Alzheimer Cognitive Composite.<br><br><strong>Results:&nbsp;<\/strong>Across the 5 cohorts, there were a total of 1292 participants (63.6% women; mean age, 70.6 [SD, 6.4] years) with tau PET assessments. Compared with men, women had significantly higher baseline p-tau217 levels at higher aggregated A\u03b2 Centiloid levels (\u03b2, -0.21 [95% CI, -0.37 to -0.05], P = .009; highest interaction was found in the Anti-Amyloid Treatment in Asymptomatic Alzheimer&rsquo;s Disease\/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration [A4\/LEARN] cohort). The sex \u00d7 p-tau217 interactions at baseline were significant for 1 tau PET region in the Harvard Aging Brain Study (HABS) cohort, for 2 tau PET regions in the A4\/LEARN cohort, for 6 tau PET regions in the Wisconsin Registry of Alzheimer&rsquo;s Prevention (WRAP) cohort, and for 4 tau PET regions in the Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer&rsquo;s Disease (PREVENT-AD) cohort. Longitudinal interactions were significant for 4 tau PET regions in the A4\/LEARN cohort, for 5 tau PET regions in both the Alzheimer&rsquo;s Disease Neuroimaging Initiative (ADNI) cohort and the WRAP cohort, and for 2 PET regions in both the HABS cohort and the PREVENT-AD cohort. Compared with men, women displayed greater tau deposition and accumulation at higher p-tau217 levels. Use of a secondary model showed women with higher p-tau217 levels also exhibited faster rates of cognitive decline relative to men in the both the WRAP cohort and the ADNI cohort.<br><br><strong>Conclusion and relevance:&nbsp;<\/strong>These findings add to growing evidence that women have a differential tau response to A\u03b2 that may emerge at the point of p-tau secretion. These findings have implications for the therapeutics and diagnostics of preclinical Alzheimer disease.<\/p><\/div>\n<\/div><\/div><\/div>\n<\/div><\/div>","protected":false},"excerpt":{"rendered":"<p>Citation : Coughlan, G. T., Ourry, V., Townsend, D., Klinger, H., Brown, J. A., Cuppels, M., Betthauser, T., Langhough, R., Cody, K., Seto, M., Birkenbihl, C., Li, A., Farrell, M., Thibault, E., Kivis\u00e4kk Webb, P., Arnold, S., Rissman, R. A., Properzi, M., Schultz, A., Johnson, K., \u2026 A4 Study Team, the Alzheimer\u2019s Disease Neuroimaging Initiative, [&hellip;]<\/p>","protected":false},"author":6,"featured_media":3430,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_eb_attr":"","_uag_custom_page_level_css":"","site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"disabled","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_themeisle_gutenberg_block_has_review":false,"footnotes":""},"categories":[24,9],"tags":[15],"class_list":["post-3351","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-24","category-publication-scientifique","tag-publications-scientifiques"],"uagb_featured_image_src":{"full":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png",300,300,false],"thumbnail":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2-150x150.png",150,150,true],"medium":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png",300,300,false],"medium_large":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png",300,300,false],"large":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png",300,300,false],"1536x1536":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png",300,300,false],"2048x2048":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2.png",300,300,false],"trp-custom-language-flag":["https:\/\/www.centre-stopad.com\/wp-content\/uploads\/2025\/03\/Journal-Medical-Streamline-Bootstrap-2-12x12.png",12,12,true]},"uagb_author_info":{"display_name":"Nolan-Patrick Cunningham","author_link":"https:\/\/www.centre-stopad.com\/en\/author\/nolan-patrick-cunningham\/"},"uagb_comment_info":0,"uagb_excerpt":"Citation : Coughlan, G. T., Ourry, V., Townsend, D., Klinger, H., Brown, J. A., Cuppels, M., Betthauser, T., Langhough, R., Cody, K., Seto, M., Birkenbihl, C., Li, A., Farrell, M., Thibault, E., Kivis\u00e4kk Webb, P., Arnold, S., Rissman, R. A., Properzi, M., Schultz, A., Johnson, K., \u2026 A4 Study Team, the Alzheimer\u2019s Disease Neuroimaging Initiative,&hellip;","_links":{"self":[{"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/posts\/3351","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/comments?post=3351"}],"version-history":[{"count":3,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/posts\/3351\/revisions"}],"predecessor-version":[{"id":3440,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/posts\/3351\/revisions\/3440"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/media\/3430"}],"wp:attachment":[{"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/media?parent=3351"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/categories?post=3351"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.centre-stopad.com\/en\/wp-json\/wp\/v2\/tags?post=3351"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}