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Whether these diagnostic strategies result in distinct profiles of molecular abnormalities is poorly understood. Here, we analysed one of the most commonly used AD omics datasets in the literature from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort and compared the two diagnosis strategies using brain transcriptome and metabolome by grouping individuals as non\u2010AD and AD according to clinical or neuropathological diagnosis separately. Differentially expressed genes, associated pathways related with AD hallmarks and AD\u2010related genes showed that the categorization based on neuropathological diagnosis more accurately reflects the disease state at the molecular level than the categorization based on clinical diagnosis. We further identified consensus biomarker candidates between the two diagnosis strategies such as 5\u2010hydroxylysine, sphingomyelin and 1\u2010myristoyl\u20102\u2010palmitoyl\u2010GPC as metabolite biomarkers and sphingolipid metabolism as a pathway biomarker, which could be robust AD biomarkers since they are independent of diagnosis strategies. We also used consensus AD and consensus non\u2010AD individuals between the two diagnostic strategies to train a machine\u2010learning based model, which we used to classify the individuals who were cognitively normal but diagnosed as AD based on neuropathological diagnosis (asymptomatic AD individuals). The majority of these individuals were classified as consensus AD patients for both omics data types. Our study provides a detailed characterization of both diagnostic strategies in terms of the association of the corresponding multi\u2010omics profiles with AD.<\/jats:p>","DOI":"10.1111\/ejn.16482","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T02:49:53Z","timestamp":1722221393000},"page":"4922-4936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multi\u2010omics analyses highlight molecular differences between clinical and neuropathological diagnoses in Alzheimer's disease"],"prefix":"10.1111","volume":"60","author":[{"given":"Hatice B\u00fc\u015fra","family":"L\u00fcleci","sequence":"first","affiliation":[{"name":"Department of Bioengineering Gebze Technical University  Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Attila","family":"Jones","sequence":"additional","affiliation":[{"name":"Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging National Institutes of Health  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tunahan","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Gebze Technical University  Kocaeli Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.966933"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15044"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100138"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadm.2019.07.002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12714"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31824b211b"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179939"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.2.198"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010933404324"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-022-00963-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.10.014"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1533317513500838"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12505"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00598"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0277-3"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.142"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.620348"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12167"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1214932"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.690372"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30440-3"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83872-z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012487302797"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0098-2"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124485"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12468"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.074320"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0252-z"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.10.014"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.08.005"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00999-y"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.04.019"},{"key":"e_1_2_10_36_1","volume-title":"The caret package","author":"Kuhn M.","year":"2012"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.966877"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00242.2007"},{"key":"e_1_2_10_39_1","first-page":"173","volume-title":"Methods in molecular biology","author":"L\u00fcleci H. 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