{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:14:44Z","timestamp":1790018084908,"version":"4.0.1"},"reference-count":76,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["101053962"],"award-info":[{"award-number":["101053962"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2019\u201002397"],"award-info":[{"award-number":["2019\u201002397"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P\u2010tau181), a recognised AD biomarker, has been described to reflect early\u2010stage cortical amyloid\u2010\u03b2 (A\u03b2) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P\u2010tau181 at the pre\u2010clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P\u2010tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted\u2010mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)\u2010A\u03b2 load. In addition, the P\u2010tau181\u2010linked metabolites were evaluated for cognitive performance and neuroimaging markers of AD and the potential to distinguish between CN A\u03b2\u2212 and CN A\u03b2+ individuals. Significant positive associations of medium\u2010 and long\u2010chain acylcarnitines (ACs) were observed with P\u2010tau181 in the entire cohort, CN A\u03b2\u2212 and CN A\u03b2+, suggesting a link between initial A\u03b2 pathology and fatty acid oxidation\u2010mediated energy metabolism pathways. However, in CN A\u03b2\u2212, additional linear associations of P\u2010tau181 were observed with muscle metabolism and nitric oxide homeostasis\u2010associated metabolites. Upon investigating the P\u2010tau181\u2010linked metabolites for cognitive performance, significant inverse correlations of the verbal and visual episodic memory and the global composite score were noted in CN A\u03b2+ with medium\u2010 and long\u2010chain ACs, suggesting prognostic value of ACs accompanying weaker cognitive performance. While investigating neuroimaging markers, ACs had positive associations with PET\u2010A\u03b2 load and inverse associations with hippocampal volume in CN A\u03b2+, indicating connections of ACs with initial AD pathogenesis. Furthermore, based on receiver operating characteristics analysis, the associated ACs potentially classified PET\u2010A\u03b2 status in older adults. Therefore, plasma P\u2010tau181\u2010linked circulating ACs may serve as potential prognostic markers for initial AD pathogenesis in CN older adults. However, further cross\u2010sectional and longitudinal research in highly characterised AD cohorts is needed to validate current findings.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16244-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16244","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T06:46:47Z","timestamp":1730270807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Circulating medium\u2010 and long\u2010chain acylcarnitines are associated with plasma P\u2010tau181 in cognitively normal older adults"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5496-0670","authenticated-orcid":false,"given":"Tahmida","family":"Sharmin","sequence":"first","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"},{"name":"Department of Pharmacy University of Rajshahi  Rajshahi Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-1958","authenticated-orcid":false,"given":"Pratishtha","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"},{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2863-0293","authenticated-orcid":false,"given":"James D.","family":"Doecke","sequence":"additional","affiliation":[{"name":"Australian eHealth Research Centre CSIRO  Brisbane Queensland Australia"},{"name":"School of Medical and Health Sciences Edith Cowan University  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Old Age Psychiatry, Institute of Psychiatry, Psychology &amp; Neuroscience King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Huynh","sequence":"additional","affiliation":[{"name":"Metabolomics Laboratory Baker Heart and Diabetes Institute  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6409-8022","authenticated-orcid":false,"given":"Steve","family":"Pedrini","sequence":"additional","affiliation":[{"name":"School of Medical and Health Sciences Edith Cowan University  Perth Western Australia Australia"},{"name":"Alzheimer's Research Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid R.","family":"Sohrabi","sequence":"additional","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"},{"name":"Alzheimer's Research Australia  Nedlands Western Australia Australia"},{"name":"School of Psychology Murdoch University  Murdoch Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Heng","sequence":"additional","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Eslick","sequence":"additional","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  Gothenburg Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology, Queen Square  London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases Clear Water Bay  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manohar","family":"Garg","sequence":"additional","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-9363","authenticated-orcid":false,"given":"Ralph N.","family":"Martins","sequence":"additional","affiliation":[{"name":"Macquarie Medical School Macquarie University  Macquarie Park New South Wales Australia"},{"name":"School of Medical and Health Sciences Edith Cowan University  Perth Western Australia Australia"},{"name":"Alzheimer's Research Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12638"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010021\u201002275\u20106"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(94)90013\u20102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(90)90255\u2010a"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010023\u201000380\u20107"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11030151"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.04.033"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010019\u20100132\u20106"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.01.019"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15128"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010180025"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12447"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12724"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450\u2010199910000\u201000013"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0155694"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1017\/s1041610292000991"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000408"},{"key":"e_1_2_10_20_1","volume-title":"Delis\u2010Kaplan executive function system (D\u2010KEFS)","author":"Delis D. C.","year":"2001"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1019800703683"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205013666160314150501"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01109053"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/gps.1010"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010017\u20102288\u20107"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20103956(75)90026\u20106"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201011118\u20107"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.146"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30028\u20100"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww139"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1254382"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010010\u20109061\u20102"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.03.009"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2009.08.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010023\u201006279\u20100"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u201000923\u2010z"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30071\u20105"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2016.31.1.7"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathmechdis\u2010030421\u2010112756"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2023.123686"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30087"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.01.023"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062897"},{"key":"e_1_2_10_44_1","volume-title":"Manual for the depression anxiety stress scales","author":"Lovibond S. H.","year":"1995"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017797\u2010x"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201002551\u2010x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3466"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz2387"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010215639"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_10_51_1","volume-title":"Rey complex figure test and recognition trial (RCFT)","author":"Meyers J. E.","year":"1995"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201019670\u2010y"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-79948-3_876"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000805"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-809633-8.20252-5"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001399\u20103"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181614289"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.23.9.1312"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318230208a"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.02.004"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1076\/clin.14.4.526.7204"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2010.06807.x"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12\u20100466"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.115.161927"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010021\u201001709\u20109"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12283"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2011.11.009"},{"key":"e_1_2_10_68_1","volume-title":"A compendium of neuropsychological tests: Administration, norms and commentary","author":"Strauss E.","year":"2006"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010020\u20100762\u20102"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.01.020"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.700587"},{"key":"e_1_2_10_72_1","volume-title":"Wechsler memory scale\u2014Revised","author":"Wechsler D.","year":"1987"},{"key":"e_1_2_10_73_1","volume-title":"Wechsler adult intelligence scale\u2010III (WAIS\u2010III) administration and scoring manual","author":"Wechsler D.","year":"1997"},{"key":"e_1_2_10_74_1","volume-title":"Wechsler test of adult reading: Examiner's manual","author":"Wechsler D.","year":"2001"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00719"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2018"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084777"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.16244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:21:28Z","timestamp":1761070888000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.16244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":76,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/jnc.16244"],"URL":"https:\/\/doi.org\/10.1111\/jnc.16244","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/JNC.16244\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.16244\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.16244\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/JNC.16244\/v2\/response1","asserted-by":"object"}]},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]},"assertion":[{"value":"2024-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jnc.16244"}}