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These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with\n                    <jats:italic>APOE<\/jats:italic>\n                    ,\n                    <jats:italic>CR1<\/jats:italic>\n                    ,\n                    <jats:italic>GMNC\/CCDC50<\/jats:italic>\n                    and\n                    <jats:italic>C16orf95\/MAP1LC3B<\/jats:italic>\n                    . Novel loci include\n                    <jats:italic>BIN1<\/jats:italic>\n                    for amyloid beta and\n                    <jats:italic>GNA12, MS4A6A, SLCO1A2<\/jats:italic>\n                    with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near\n                    <jats:italic>ANGPT1<\/jats:italic>\n                    and chr. 9 near\n                    <jats:italic>SMARCA2<\/jats:italic>\n                    . We also demonstrate that these variants have significant association with Alzheimer\u2019s disease risk, disease progression and\/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of\n                    <jats:italic>APOE<\/jats:italic>\n                    , coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-71682-8","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:46:44Z","timestamp":1776772004000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["GWAS meta-analysis of cerebrospinal fluid Alzheimer\u2019s biomarkers reveals loci regulating lipids, brain volume and 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C.C. is a member of the advisory board of Circular Genomics and owns stocks in these companies. C.C. is part of the advisory board of ADmit. DMH is a co-founder and has equity in C2N Diagnostics. He is on the scientific advisory board of C2N Diagnostics, Denali, Genentech, Switch Therapeutics, Acta Pharmaceuticals, and Cajal Neurosciences. He consults for Pfizer, AbbVie, and Roche. MWN, FT, and YW are employees of Eisai. H.H. is an employee of Eisai Inc.; however, this article does not represent the opinion of Eisai. His contribution to this article reflects exclusively his academic and scientific expertise developed as part of an academic position at Sorbonne University, Paris, France. H.H. serves as Reviewing Editor and previously as Senior Associate Editor for the journal Alzheimer\u2019s & Dementia, the journal of the Alzheimer\u2019s Association. Part of this study was initiated and developed in line with the Alzheimer\u2019s Precision Medicine Initiative (APMI) framework. H.H. declares no competing financial interests related to the present article. QSL was an employee of Janssen Research & Development, LLC when the work was conducted, and owns company stocks. S.K. has served at scientific advisory boards, speaker and\/or as consultant for Roche, Eli Lilly, Geras Solutions, Optoceutics, Biogen, Eisai, Merry Life, Triolab, Novo Nordisk and Bioarctic, unrelated to present study content. H.Z. has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). K.B. has served as a consultant and at advisory boards for Abbvie, AC Immune, ALZPath, AriBio, Beckman-Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. M.B. has consulted for Grifols, Araclon Biotech, Roche, Biogen, Lilly, Merck, Novo-Nordisk; has served in the Advisory Boards from Grifols, Roche, Lilly, Araclon Biotech, Merck, Biogen, Novo-Nordisk, Bioiberica, Eisai, Servier, Schwabe Pharma; received fees from lectures from Roche, Biogen, Grifols, Nutricia, Araclon Biotech, Novo-Nordisk, Eisai, Terumo, Schwabe Pharma; and reports research funding from Life Molecular Imaging, Bioiberica, Grifols, Araclon Biotech, Lilly, Roche, Janssen, Alzehon, Cortyzime, Novo Nordisk, Schwabe Pharma. M.M. has consulted for F. Hoffmann-La Roche Ltd. and has served in the Spanish Scientific Advisory Board for biomarkers of Araclon Biotech. R.V.\u2019s institution has clinical trial agreements (R.V. as PI) with Alector, AviadoBio, Biogen, BMS, Denali, EliLilly, J&J and UCB. R.V.\u2019s institution has a consultancy agreement (R.V. as DSMB or DMC member) with AC Immune and Novartis. A.H. has acted as a consultant for Quanterix. CR is founder and majority shareholder at Scottish Brain Sciences. C.R. received Compensation for study-related activities on a per-patient per-visit basis by AC Immune SA to his institution. C.R. receives consulting fees from Biogen, Eisai, MSD, Actinogen, Roche, Eli Lilly, Novo Nordisk. S.E. received research grants from EU Innovative Health Initiative (IHI), Interreg Vlaanderen-Nederland, EU Erasmus+ programme, Research Foundation Flanders (FWO), VLAIO, GSKE\/FMRE (paid to institution), consulting fees from Icometrix, Novartis, Eisai (paid to institution), personal consulting fees from Roche and Biogen, personal honoraria from Eisai, Roche, travel support to institution from Biogen, Patent EP3452830B1 (institution), member of SMB\/SAB for EU-H2020 project RECAGE (unpaid) and member of DSMB of PRImus-AD (unpaid), VP of Belgian Dementia Council (unpaid) and co-chair of European Alzheimer Disease Consortium (EADC) (unpaid).LMS has served as a consultant and on advisory boards for Biogen and Roche; has received honoraria for lectures and presentations from Biogen and Roche. S.E.S. has served on scientific advisory boards on biomarker testing and clinical care pathways for Eisai and Novo Nordisk and has received speaking fees for presentations on biomarker testing from Eisai, Eli Lilly, and Novo Nordisk. T.J.H. served as a Scientific Advisor for Vivid Genomics, serves as Deputy Editor for Alzheimer\u2019s & Dementia: TRCI, and serves as Senior Associate Editor for Alzheimer\u2019s & Dementia. A.L. has served as a consultant or on advisory boards for Almirall, Fujirebio-Europe, Roche, Biogen, Grifols, Novartis, Eisai, Lilly, and Nutricia, outside the submitted work. S.C.J. serves on advisory boards to AlzPath, Lilly and Enigma Biomedical. N.S. has been supported by NovoNordisk (local principal investigator in phase III international clinical trial; funding to the institution). The remaining authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"7385"}}