{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:47:02Z","timestamp":1791852422908,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000319","name":"Alzheimer's Research Trust","doi-asserted-by":"publisher","award":["ARUK\u2010SRF2016A\u20103 C"],"award-info":[{"award-number":["ARUK\u2010SRF2016A\u20103 C"]}],"id":[{"id":"10.13039\/501100000319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's disease (AD) is a devastating neurological disease that disproportionately affects women. This study aimed to investigate sex\u2010specific single lipids associated with AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Plasma samples from 841 participants, comprising 306 individuals with AD, 165 with mild cognitive impairment (MCI), and 370 cognitively healthy controls were curated from the AddNeuroMed cohort. Lipidomics identified 268 single lipids for each sample. We investigated sex\u2010specific associations from lipid modules and single lipids to AD and probed for causality with mediation analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Three modules associated with AD in the female subset and one in the male subset (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). In the female participants with AD, lipid families containing highly unsaturated fatty acids were reduced and those containing saturated lipids were increased (<jats:italic>q<\/jats:italic> value\u00a0&lt;\u00a00.05). The effects of unsaturated phospholipids on AD were not mediated via cholesterol, low\u2010density lipoprotein, or apolipoprotein B.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Women with AD have lower unsaturated plasma lipid levels compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Lipid profiling showed lipid changes associated with Alzheimer's disease (AD) exclusively in women.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Women with AD had fewer highly unsaturated lipids and more saturated lipids.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Unsaturated phospholipids affected AD independently of cholesterol, low\u2010density lipoprotein, or apolipoprotein B.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sex\u2010stratified analysis is key to understanding the different manifestations of AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70512","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T11:00:27Z","timestamp":1755687627000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lipid profiling reveals unsaturated lipid reduction in women with Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Asger","family":"Wretlind","sequence":"first","affiliation":[{"name":"King's College London  London UK"},{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[{"name":"King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latha","family":"Velayudhan","sequence":"additional","affiliation":[{"name":"King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Diseases UCL Institute of Neurology  London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petroula","family":"Proitsi","sequence":"additional","affiliation":[{"name":"King's College London  London UK"},{"name":"Centre for Preventive Neurology, Wolfson Institute of Population Health Queen Mary University London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Legido\u2010Quigley","sequence":"additional","affiliation":[{"name":"King's College London  London UK"},{"name":"Steno Diabetes Center Copenhagen  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.10.005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12362.Population"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11398"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010180141.Differences"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.01.024"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44294\u2010024\u201000021\u20103"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003615"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9111610"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201014959\u2010w"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00241"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.318247"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000731\u20101"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fradi.2022.782864"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(24)01296\u20100"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.2009.05064.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00741-z"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_11_19_1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"Barrio V","year":"2004"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2412\u2010a"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.56.3.303"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3744\/snak.2003.40.2.021"},{"key":"e_1_2_11_23_1","first-page":"236","article-title":"The Alzheimer \u2019 s disease assessment scale\u2014cognitive subscale","volume":"8","author":"Mohs RC","year":"1996","journal-title":"Iniernnfional Psychogeriatrics"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010111"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5930.Genetic"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac300716u"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21540"},{"key":"e_1_2_11_29_1","unstructured":"Core TeamR (2018).R: A language and environment for statistical computing.2018."},{"key":"e_1_2_11_30_1","unstructured":"YoshidaK BartelA ChipmanJJ et\u00a0al.R Package \u2018 tableone\u2019: Create \u201cTable 1\u201d to Describe Baseline Characteristics with or without Propensity Score Weights2022."},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-020-00215-0"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12961"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u20109\u2010559"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v059.i05"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201003279\u2010x"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014279\u20108"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201002931\u2010w"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010191304"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5378540"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665108005983"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcab085"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002266"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adc9317"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X15611678"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010017\u20100237\u2010y"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.844066"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010022\u201001121\u20105"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201030875\u20107"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1044-1"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.730829"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2019.04.003"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.5551\/jat.14.12"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(95)00931\u2010F"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u20102011\u2010101608"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2015.05.003"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13241"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70512","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:36:34Z","timestamp":1759955794000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70512"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":55,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/alz.70512"],"URL":"https:\/\/doi.org\/10.1002\/alz.70512","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70512"}}