{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:55:18Z","timestamp":1781801718530,"version":"3.54.5"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-026-05978-7","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T14:40:57Z","timestamp":1781793657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling Aberrant Metabolic Patterns in Alzheimer\u2019s Disease Subtypes: From Perturbed Metabolic Pathways to Candidate Drug Targets"],"prefix":"10.1007","volume":"63","author":[{"given":"Hatice B\u00fc\u015fra","family":"L\u00fcleci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan A.","family":"Neff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunahan","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav","family":"Thambisetty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"5978_CR1","first-page":"1","volume":"1","author":"CL Masters","year":"2015","unstructured":"Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL (2015) Alzheimer\u2019s disease. Nat Rev Dis Prim 1:1\u201318","journal-title":"Nat Rev Dis Prim"},{"key":"5978_CR2","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.bbadis.2016.03.001","volume":"1862","author":"J Xu","year":"2016","unstructured":"Xu J, Begley P, Church SJ, Patassini S, Hollywood KA, J\u00fcllig M, Curtis MA, Waldvogel HJ et al (2016) Graded perturbations of metabolism in multiple regions of human brain in Alzheimer\u2019s disease: snapshot of a pervasive metabolic disorder. Biochimica et Biophysica Acta (BBA) 1862:1084\u20131092","journal-title":"Biochimica et Biophysica Acta (BBA)"},{"key":"5978_CR3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003012","volume":"17","author":"UV Mahajan","year":"2020","unstructured":"Mahajan UV, Varma VR, Griswold ME, Blackshear CT, An Y, Oommen AM, Varma S, Troncoso JC et al (2020) Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: a targeted metabolomic and transcriptomic study. PLoS Med 17:e1003012","journal-title":"PLoS Med"},{"key":"5978_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41514-021-00064-9","volume":"7","author":"VR Varma","year":"2021","unstructured":"Varma VR, L\u00fcleci HB, Oommen AM, Varma S, Blackshear CT, Griswold ME, An Y, Roberts JA et al (2021) Abnormal brain cholesterol homeostasis in Alzheimer\u2019s disease\u2014a targeted metabolomic and transcriptomic study. npj Aging Mech Dis 7:1\u201314","journal-title":"npj Aging Mech Dis"},{"key":"5978_CR5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s00401-020-02152-8","volume":"140","author":"TG Demarest","year":"2020","unstructured":"Demarest TG, Varma VR, Estrada D, Babbar M, Basu S, Mahajan UV, Moaddel R, Croteau DL et al (2020) Biological sex and DNA repair deficiency drive Alzheimer\u2019s disease via systemic metabolic remodeling and brain mitochondrial dysfunction. Acta Neuropathol 140:25\u201347","journal-title":"Acta Neuropathol"},{"key":"5978_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003615","volume":"18","author":"VR Varma","year":"2021","unstructured":"Varma VR, Wang Y, An Y, Varma S, Bilgel M, Doshi J, Legido-Quigley C, Delgado JC et al (2021) Bile acid synthesis, modulation, and dementia: a metabolomic, transcriptomic, and pharmacoepidemiologic study. PLoS Med 18:e1003615","journal-title":"PLoS Med"},{"key":"5978_CR7","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41583-019-0132-6","volume":"20","author":"DA Butterfield","year":"2019","unstructured":"Butterfield DA, Halliwell B (2019) Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci 20:148\u2013160","journal-title":"Nat Rev Neurosci"},{"key":"5978_CR8","doi-asserted-by":"publisher","first-page":"3489","DOI":"10.1111\/bph.14585","volume":"176","author":"JM Perez Ortiz","year":"2019","unstructured":"Perez Ortiz JM, Swerdlow RH (2019) Mitochondrial dysfunction in Alzheimer\u2019s disease: role in pathogenesis and novel therapeutic opportunities. Br J Pharmacol 176:3489\u20133507","journal-title":"Br J Pharmacol"},{"key":"5978_CR9","doi-asserted-by":"crossref","unstructured":"Yin F (2023) Lipid metabolism and Alzheimer\u2019s disease: clinical evidence, mechanistic link and therapeutic promise. The FEBS Journal 290(6):1420\u20131453","DOI":"10.1111\/febs.16344"},{"key":"5978_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/srep02364","volume":"3","author":"K Inoue","year":"2013","unstructured":"Inoue K, Tsutsui H, Akatsu H, Hashizume Y, Matsukawa N, Yamamoto T, Toyo\u2019Oka T (2013) Metabolic profiling of Alzheimer\u2019s disease brains. Sci Rep 3:2364","journal-title":"Sci Rep"},{"key":"5978_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00702-021-02449-2","volume":"129","author":"KA Jellinger","year":"2022","unstructured":"Jellinger KA (2022) Recent update on the heterogeneity of the Alzheimer\u2019s disease spectrum. J Neural Transm 129:1\u201324","journal-title":"J Neural Transm"},{"key":"5978_CR12","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo6764","volume":"8","author":"Y Iturria-Medina","year":"2022","unstructured":"Iturria-Medina Y, Adewale Q, Khan AF, Ducharme S, Rosa-Neto P, O\u2019Donnell K, Petyuk VA, Gauthier S, et al. (2022) Unified epigenomic, transcriptomic, proteomic, and metabolomic taxonomy of Alzheimer\u2019s disease progression and heterogeneity. Sci Adv 8:eabo6764","journal-title":"Sci Adv"},{"key":"5978_CR13","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb5398","volume":"7","author":"RA Neff","year":"2021","unstructured":"Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Wang E, Horgusluoglu-Moloch E et al (2021) Molecular subtyping of Alzheimer\u2019s disease using RNA sequencing data reveals novel mechanisms and targets. Sci Adv 7:eabb5398","journal-title":"Sci Adv"},{"key":"5978_CR14","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101638","volume":"10","author":"D Ferreira","year":"2018","unstructured":"Ferreira D, Wahlund L-O, Westman E (2018) The heterogeneity within Alzheimer\u2019s disease. Aging (Albany NY) 10:3058","journal-title":"Aging (Albany NY)"},{"key":"5978_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms3632","volume":"4","author":"K Yizhak","year":"2013","unstructured":"Yizhak K, Gabay O, Cohen H, Ruppin E (2013) Model-based identification of drug targets that revert disrupted metabolism and its application to ageing. Nat Commun 4:1\u201311","journal-title":"Nat Commun"},{"key":"5978_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05116-5","volume":"9","author":"F Cheng","year":"2018","unstructured":"Cheng F, Desai RJ, Handy DE, Wang R, Schneeweiss S, Barab\u00e1si A-L, Loscalzo J (2018) Network-based approach to prediction and population-based validation of in silico drug repurposing. Nat Commun 9:2691","journal-title":"Nat Commun"},{"key":"5978_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/sdata.2018.185","volume":"5","author":"M Wang","year":"2018","unstructured":"Wang M, Beckmann ND, Roussos P, Wang E, Zhou X, Wang Q, Ming C, Neff R et al (2018) The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer\u2019s disease. Sci Data 5:1\u201316","journal-title":"Sci Data"},{"key":"5978_CR18","doi-asserted-by":"publisher","first-page":"S161","DOI":"10.3233\/JAD-179939","volume":"64","author":"DA Bennett","year":"2018","unstructured":"Bennett DA, Buchman AS, Boyle PA, Barnes LL, Wilson RS, Schneider JA (2018) Religious orders study and Rush Memory and Aging Project. J Alzheimers Dis 64:S161\u2013S189","journal-title":"J Alzheimers Dis"},{"key":"5978_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/sdata.2018.142","volume":"5","author":"PL De Jager","year":"2018","unstructured":"De Jager PL, Ma Y, McCabe C, Xu J, Vardarajan BN, Felsky D, Klein H-U, White CC et al (2018) A multi-omic atlas of the human frontal cortex for aging and Alzheimer\u2019s disease research. Sci Data 5:1\u201313","journal-title":"Sci Data"},{"key":"5978_CR20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/01.JGP.0000192478.82189.a8","volume":"14","author":"R Perneczky","year":"2006","unstructured":"Perneczky R, Wagenpfeil S, Komossa K, Grimmer T, Diehl J, Kurz A (2006) Mapping scores onto stages: Mini-Mental State Examination and Clinical Dementia Rating. Am J Geriatr Psychiatry 14:139\u2013144","journal-title":"Am J Geriatr Psychiatry"},{"key":"5978_CR21","doi-asserted-by":"crossref","unstructured":"Robinson JL, Kocaba\u015f P, Wang H, Cholley PE, Cook D, Nilsson A, Anton M, Ferreira R et al (2020) An atlas of human metabolism. Sci Signal 13(624)","DOI":"10.1126\/scisignal.aaz1482"},{"key":"5978_CR22","doi-asserted-by":"publisher","first-page":"3140","DOI":"10.1093\/bioinformatics\/btq602","volume":"26","author":"H Zur","year":"2010","unstructured":"Zur H, Ruppin E, Shlomi T (2010) iMAT: an integrative metabolic analysis tool. Bioinformatics 26:3140\u20133142","journal-title":"Bioinformatics"},{"key":"5978_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003580","volume":"10","author":"D Machado","year":"2014","unstructured":"Machado D, Herrg\u00e5rd M (2014) Systematic evaluation of methods for integration of transcriptomic data into constraint-based models of metabolism. PLoS Comput Biol 10:e1003580","journal-title":"PLoS Comput Biol"},{"key":"5978_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-024-05845-z","volume":"25","author":"L Fresnais","year":"2024","unstructured":"Fresnais L, Perin O, Riu A, Grall R, Ott A, Fromenty B, Gallardo J-C, Stingl M et al (2024) A strategy to detect metabolic changes induced by exposure to chemicals from large sets of condition-specific metabolic models computed with enumeration techniques. BMC Bioinformatics 25:234","journal-title":"BMC Bioinformatics"},{"key":"5978_CR25","doi-asserted-by":"publisher","unstructured":"L\u00fcleci HB, Uzuner D, \u00c7ak\u0131r T, Thambisetty M (2023) Computational approaches to assess abnormal metabolism in Alzheimer\u2019s disease using transcriptomics. Methods Mol. Biol. Springer, pp 173\u2013189. https:\/\/doi.org\/10.1007\/978-1-0716-2655-9_9","DOI":"10.1007\/978-1-0716-2655-9_9"},{"key":"5978_CR26","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41596-018-0098-2","volume":"14","author":"L Heirendt","year":"2019","unstructured":"Heirendt L, Arreckx S, Pfau T, Mendoza SN, Richelle A, Heinken A, Haraldsd\u00f3ttir HS, Wachowiak J et al (2019) Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v. 3.0. Nat Protoc 14:639\u2013702","journal-title":"Nat Protoc"},{"key":"5978_CR27","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1214\/10-AOAS327","volume":"4","author":"S Lee","year":"2010","unstructured":"Lee S, Huang JZ, Hu J (2010) Sparse logistic principal components analysis for binary data. Ann Appl Stat 4:1579","journal-title":"Ann Appl Stat"},{"key":"5978_CR28","doi-asserted-by":"publisher","DOI":"10.1201\/9780429447273","volume-title":"Interactive web-based data visualization with R, plotly, and shiny","author":"C Sievert","year":"2020","unstructured":"Sievert C (2020) Interactive web-based data visualization with R, plotly, and shiny. CRC Press"},{"key":"5978_CR29","first-page":"1","volume":"18","author":"S Balakrishnama","year":"1998","unstructured":"Balakrishnama S, Ganapathiraju A (1998) Linear discriminant analysis-a brief tutorial. Inst Signal Inf Process 18:1\u20138","journal-title":"Inst Signal Inf Process"},{"key":"5978_CR30","first-page":"19","volume":"3","author":"MK Vijaymeena","year":"2016","unstructured":"Vijaymeena MK, Kavitha K (2016) A survey on similarity measures in text mining. Mach Learn Appl An Int J 3:19\u201328","journal-title":"Mach Learn Appl An Int J"},{"key":"5978_CR31","volume-title":"The genetical theory of natural selection","author":"RA Fisher","year":"1958","unstructured":"Fisher RA (1958) The genetical theory of natural selection. P\u0438\u043fo\u043b \u041a\u043bacc\u0438\u043a"},{"key":"5978_CR32","doi-asserted-by":"crossref","unstructured":"Baloni P, Funk CC, Yan J, Yurkovich JT, Kueider-Paisley A, Nho K, Heinken A, Jia W, Mahmoudiandehkordi S, Louie G et al (2019) Identifying differences in bile acid pathways for cholesterol clearance in Alzheimer\u2019s disease using metabolic networks of human brain regions. BioRxiv 782987","DOI":"10.1101\/782987"},{"key":"5978_CR33","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.ymben.2003.09.002","volume":"5","author":"R Mahadevan","year":"2003","unstructured":"Mahadevan R, Schilling CH (2003) The effects of alternate optimal solutions in constraint-based genome-scale metabolic models. Metab Eng 5:264\u2013276","journal-title":"Metab Eng"},{"key":"5978_CR34","doi-asserted-by":"publisher","first-page":"4350","DOI":"10.1093\/bioinformatics\/btz231","volume":"35","author":"LV Valc\u00e1rcel","year":"2019","unstructured":"Valc\u00e1rcel LV, Torrano V, Tobalina L, Carracedo A, Planes FJ (2019) rMTA: robust metabolic transformation analysis. Bioinformatics 35:4350\u20134355","journal-title":"Bioinformatics"},{"key":"5978_CR35","doi-asserted-by":"publisher","first-page":"D668","DOI":"10.1093\/nar\/gkj067","volume":"34","author":"DS Wishart","year":"2006","unstructured":"Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, Chang Z, Woolsey J (2006) DrugBank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res 34:D668\u2013D672","journal-title":"Nucleic Acids Res"},{"key":"5978_CR36","doi-asserted-by":"crossref","unstructured":"Novotny BC, Fernandez MV, Wang C, Budde JP, Bergmann K, Eteleeb AM, Bradley J, Webster C, et al (2023) Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer\u2019s disease brains. Alzheimer\u2019s Dement 19:1785\u20131799","DOI":"10.1002\/alz.12800"},{"key":"5978_CR37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041249","volume":"21","author":"JA Roberts","year":"2020","unstructured":"Roberts JA, Varma VR, Huang C-W, An Y, Oommen A, Tanaka T, Ferrucci L, Elango P et al (2020) Blood metabolite signature of metabolic syndrome implicates alterations in amino acid metabolism: findings from the Baltimore Longitudinal Study of Aging (BLSA) and the Tsuruoka Metabolomics Cohort Study (TMCS). Int J Mol Sci 21:1249","journal-title":"Int J Mol Sci"},{"key":"5978_CR38","doi-asserted-by":"publisher","first-page":"W207","DOI":"10.1093\/nar\/gkad347","volume":"51","author":"L Kolberg","year":"2023","unstructured":"Kolberg L, Raudvere U, Kuzmin I, Adler P, Vilo J, Peterson H (2023) g: Profiler\u2014interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update). Nucleic Acids Res 51:W207\u2013W212","journal-title":"Nucleic Acids Res"},{"key":"5978_CR39","unstructured":"Niwattanakul S, Singthongchai J, Naenudorn E, Wanapu S (2013) Using of Jaccard coefficient for keywords similarity. In: Proc. Int. Multiconference Eng. Comput. Sci pp. 380\u2013384"},{"key":"5978_CR40","doi-asserted-by":"publisher","first-page":"4238","DOI":"10.1021\/jm00100a032","volume":"35","author":"MR Pavia","year":"1992","unstructured":"Pavia MR, Lobbestael SJ, Nugiel D, Mayhugh DR, Gregor VE, Taylor CP, Schwarz RD, Brahce L et al (1992) Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake. J Med Chem 35:4238\u20134248","journal-title":"J Med Chem"},{"key":"5978_CR41","doi-asserted-by":"crossref","unstructured":"Batra R, Arnold M, W\u00f6rheide MA, Allen A, Wang X, Blach C, Levey AI, Seyfried NT, et al (2023) The landscape of metabolic brain alterations in Alzheimer\u2019s disease. Alzheimer\u2019s\u00a0 Dement 19:980\u2013998","DOI":"10.1002\/alz.12714"},{"key":"5978_CR42","doi-asserted-by":"crossref","unstructured":"Morgan SL, Naderi P, Koler K, Pita-Juarez Y, Prokopenko D, Vlachos IS, Tanzi RE, Bertram L et al (2022) Most pathways can be related to the pathogenesis of Alzheimer\u2019s disease. Front Aging Neurosci 14:846902","DOI":"10.3389\/fnagi.2022.846902"},{"key":"5978_CR43","doi-asserted-by":"crossref","unstructured":"MahmoudianDehkordi S, Arnold M, Nho K, Ahmad S, Jia W, Xie G, Louie G, Kueider-Paisley A, et al (2019) Altered bile acid profile associates with cognitive impairment in Alzheimer\u2019s disease\u2014an emerging role for gut microbiome. Alzheimer\u2019s\u00a0 Dement 15:76\u201392","DOI":"10.1016\/j.jalz.2018.07.217"},{"key":"5978_CR44","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102328","volume":"11","author":"A Pesini","year":"2019","unstructured":"Pesini A, Iglesias E, Bayona-Bafaluy MP, Garrido-P\u00e9rez N, Meade P, Gaud\u00f3 P, Jim\u00e9nez-Salvador I, Andr\u00e9s-Benito P et al (2019) Brain pyrimidine nucleotide synthesis and Alzheimer disease. Aging (Albany NY) 11:8433","journal-title":"Aging (Albany NY)"},{"key":"5978_CR45","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.580001","volume":"12","author":"J Killingsworth","year":"2021","unstructured":"Killingsworth J, Sawmiller D, Shytle RD (2021) Propionate and Alzheimer\u2019s disease. Front Aging Neurosci 12:580001","journal-title":"Front Aging Neurosci"},{"key":"5978_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12964-021-00715-0","volume":"19","author":"SE Desale","year":"2021","unstructured":"Desale SE, Chinnathambi S (2021) Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer\u2019s disease. Cell Commun Signal 19:1\u201312","journal-title":"Cell Commun Signal"},{"key":"5978_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01464","volume":"8","author":"RA Whittington","year":"2017","unstructured":"Whittington RA, Planel E, Terrando N (2017) Impaired resolution of inflammation in Alzheimer\u2019s disease: a review. Front Immunol 8:1464","journal-title":"Front Immunol"},{"key":"5978_CR48","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.drudis.2018.09.008","volume":"24","author":"J Michael","year":"2019","unstructured":"Michael J, Marschallinger J, Aigner L (2019) The leukotriene signaling pathway: a druggable target in Alzheimer\u2019s disease. Drug Discov Today 24:505\u2013516","journal-title":"Drug Discov Today"},{"key":"5978_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13195-021-00892-7","volume":"13","author":"LY Xiong","year":"2021","unstructured":"Xiong LY, Ouk M, Wu C-Y, Rabin JS, Lanct\u00f4t KL, Herrmann N, Black SE, Edwards JD et al (2021) Leukotriene receptor antagonist use and cognitive decline in normal cognition, mild cognitive impairment, and Alzheimer\u2019s dementia. Alzheimers Res Ther 13:1\u201311","journal-title":"Alzheimers Res Ther"},{"key":"5978_CR50","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202000067","volume":"43","author":"M Hortov\u00e1-Kohoutkov\u00e1","year":"2021","unstructured":"Hortov\u00e1-Kohoutkov\u00e1 M, L\u00e1zni\u010dkov\u00e1 P, Fri\u010d J (2021) How immune-cell fate and function are determined by metabolic pathway choice: the bioenergetics underlying the immune response. BioEssays 43:2000067","journal-title":"BioEssays"},{"key":"5978_CR51","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2026.1772036","volume":"17","author":"X Xiao","year":"2026","unstructured":"Xiao X, Yan X, Liang C, Yang Y (2026) Metabolic dysfunction and mitochondrial failure in Alzheimer\u2019s disease: integrating pathophysiology, clinical evidence and emerging interventions. Front Neurol 17:1772036","journal-title":"Front Neurol"},{"key":"5978_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105799","volume":"171","author":"K Ramamoorthy","year":"2022","unstructured":"Ramamoorthy K, Yoshimura R, Al-Juburi S, Anandam KY, Kapadia R, Alachkar A, Abbott GW, Said HM (2022) Alzheimer\u2019s disease is associated with disruption in thiamin transport physiology: a potential role for neuroinflammation. Neurobiol Dis 171:105799","journal-title":"Neurobiol Dis"},{"key":"5978_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2020.101904","volume":"198","author":"S Ayton","year":"2021","unstructured":"Ayton S, Janelidze S, Roberts B, Palmqvist S, Kalinowski P, Diouf I, Belaidi AA, Stomrud E et al (2021) Acute phase markers in CSF reveal inflammatory changes in Alzheimer\u2019s disease that intersect with pathology, APOE $\\varepsilon$4, sex and age. Prog Neurobiol 198:101904","journal-title":"Prog Neurobiol"},{"key":"5978_CR54","doi-asserted-by":"crossref","unstructured":"DeKosky ST, Ikonomovic MD, Wang X, Farlow M, Wisniewski S, Lopez OL, Becker JT, Saxton J, et al (2003) Plasma and cerebrospinal fluid $\u03b1$1-antichymotrypsin levels in Alzheimer\u2019s disease: correlation with cognitive impairment. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc 53:81\u201390","DOI":"10.1002\/ana.10414"},{"key":"5978_CR55","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.cca.2019.07.022","volume":"497","author":"G Bivona","year":"2019","unstructured":"Bivona G, Lo Sasso B, Iacolino G, Gambino CM, Scazzone C, Agnello L, Ciaccio M (2019) Standardized measurement of circulating vitamin D [25 (OH) D] and its putative role as a serum biomarker in Alzheimer\u2019s disease and Parkinson\u2019s disease. Clin Chim Acta 497:82\u201387","journal-title":"Clin Chim Acta"},{"key":"5978_CR56","doi-asserted-by":"publisher","first-page":"14742","DOI":"10.1039\/D4RA01536C","volume":"14","author":"A Tahir","year":"2024","unstructured":"Tahir A, Mobeen B, Hussain F, Sadiq A, Rashid U (2024) Pregnenolone derivatives for the treatment of Alzheimer\u2019s disease: synthesis, and in vitro inhibition of amyloid $\u03b2$ 1-42 peptide aggregation, acetylcholinesterase and carbonic anhydrase-II. RSC Adv 14:14742\u201314757","journal-title":"RSC Adv"},{"key":"5978_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40364-018-0119-x","volume":"6","author":"Y Nagata","year":"2018","unstructured":"Nagata Y, Hirayama A, Ikeda S, Shirahata A, Shoji F, Maruyama M, Kayano M, Bundo M, et al. (2018) others, Comparative analysis of cerebrospinal fluid metabolites in Alzheimer\u2019s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort. Biomark Res 6:1\u201311","journal-title":"Biomark Res"},{"key":"5978_CR58","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1021\/pr5000895","volume":"13","author":"G Wang","year":"2014","unstructured":"Wang G, Zhou Y, Huang F-J, Tang H-D, Xu X-H, Liu J-J, Wang Y, Deng Y-L et al (2014) Plasma metabolite profiles of Alzheimer\u2019s disease and mild cognitive impairment. J Proteome Res 13:2649\u20132658","journal-title":"J Proteome Res"},{"key":"5978_CR59","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1001\/archpsyc.1984.01790150033006","volume":"41","author":"MA Raskind","year":"1984","unstructured":"Raskind MA, Peskind ER, Halter JB, Jimerson DC (1984) Norepinephrine and MHPG levels in CSF and plasma in Alzheimer\u2019s disease. Arch Gen Psychiatry 41:343\u2013346","journal-title":"Arch Gen Psychiatry"},{"key":"5978_CR60","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/j.dadm.2019.07.002","volume":"11","author":"DK Barupal","year":"2019","unstructured":"Barupal DK, Baillie R, Fan S, Saykin AJ, Meikle PJ, Arnold M, Nho K, Fiehn O et al (2019) Sets of coregulated serum lipids are associated with Alzheimer\u2019s disease pathophysiology. Alzheimers Dement Amst 11:619\u2013627","journal-title":"Alzheimers Dement Amst"},{"key":"5978_CR61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13024-022-00536-w","volume":"17","author":"L Bossaerts","year":"2022","unstructured":"Bossaerts L, Cacace R, Van Broeckhoven C (2022) The role of ATP-binding cassette subfamily A in the etiology of Alzheimer\u2019s disease. Mol Neurodegener 17:1\u201312","journal-title":"Mol Neurodegener"},{"key":"5978_CR62","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1084\/jem.20081588","volume":"205","author":"H Qing","year":"2008","unstructured":"Qing H, He G, Ly PTT, Fox CJ, Staufenbiel M, Cai F, Zhang Z, Wei S et al (2008) Valproic acid inhibits A<span>$<\/span>\u03b2<span>$<\/span> production, neuritic plaque formation, and behavioral deficits in Alzheimer\u2019s disease mouse models. J Exp Med 205:2781\u20132789","journal-title":"J Exp Med"},{"key":"5978_CR63","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s00210-017-1357-4","volume":"390","author":"ME Sorial","year":"2017","unstructured":"Sorial ME, El Sayed NSED (2017) Protective effect of valproic acid in streptozotocin-induced sporadic Alzheimer\u2019s disease mouse model: possible involvement of the cholinergic system. Naunyn Schmiedebergs Arch Pharmacol 390:581\u2013593","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"5978_CR64","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1007\/s12035-014-8751-4","volume":"51","author":"A-G Xuan","year":"2015","unstructured":"Xuan A-G, Pan X-B, Wei P, Ji W-D, Zhang W-J, Liu J-H, Hong L-P, Chen W-L et al (2015) Valproic acid alleviates memory deficits and attenuates amyloid-$\u03b2$ deposition in transgenic mouse model of Alzheimer\u2019s disease. Mol Neurobiol 51:300\u2013312","journal-title":"Mol Neurobiol"},{"key":"5978_CR65","doi-asserted-by":"publisher","first-page":"E1876","DOI":"10.1073\/pnas.1718819115","volume":"115","author":"Y Hou","year":"2018","unstructured":"Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E, Zhang Y, Moritoh K et al (2018) NAD+ supplementation normalizes key Alzheimer\u2019s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proceedings of the National Academy of Sciences 115:E1876\u2013E1885","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"5978_CR66","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1016\/j.neurobiolaging.2012.12.005","volume":"34","author":"B Gong","year":"2013","unstructured":"Gong B, Pan Y, Vempati P, Zhao W, Knable L, Ho L, Wang J, Sastre M et al (2013) Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-$\u03b3$ coactivator 1$\u03b1$ regulated $\u03b2$-secretase 1 degradation and mitochondrial gene expression in Alzheimer\u2019s mouse models. Neurobiol Aging 34:1581\u20131588","journal-title":"Neurobiol Aging"},{"key":"5978_CR67","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1080\/1061186X.2017.1354002","volume":"26","author":"R Aalinkeel","year":"2018","unstructured":"Aalinkeel R, Kutscher HL, Singh A, Cwiklinski K, Khechen N, Schwartz SA, Prasad PN, Mahajan SD (2018) Neuroprotective effects of a biodegradable poly (lactic-co-glycolic acid)-ginsenoside Rg3 nanoformulation: a potential nanotherapy for Alzheimer\u2019s disease? J Drug Target 26:182\u2013193","journal-title":"J Drug Target"},{"key":"5978_CR68","doi-asserted-by":"publisher","DOI":"10.1016\/j.crphar.2022.100149","volume":"4","author":"V Rani","year":"2023","unstructured":"Rani V, Verma R, Kumar K, Chawla R (2023) Role of pro-inflammatory cytokines in Alzheimer\u2019s disease and neuroprotective effects of pegylated self-assembled nanoscaffolds. Curr Res Pharmacol Drug Discov 4:100149","journal-title":"Curr Res Pharmacol Drug Discov"},{"key":"5978_CR69","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3109\/08039488.2011.605172","volume":"66","author":"M Coppola","year":"2012","unstructured":"Coppola M, Mondola R (2012) Potential action of betel alkaloids on positive and negative symptoms of schizophrenia: a review. Nord J Psychiatry 66:73\u201378","journal-title":"Nord J Psychiatry"},{"key":"5978_CR70","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1134\/S1070428022060057","volume":"58","author":"DA Lomov","year":"2022","unstructured":"Lomov DA, Abramyants MG, Zaporozhets OO, Pekhtereva TM (2022) Alternative synthesis of the alkaloid guvacine and its derivatives. Russ J Org Chem 58:791\u2013799","journal-title":"Russ J Org Chem"},{"key":"5978_CR71","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/alz.12675","volume":"19","author":"R Chang","year":"2023","unstructured":"Chang R, Trushina E, Zhu K, Zaidi SSA, Lau BM, Kueider-Paisley A, Moein S, He Q et al (2023) Predictive metabolic networks reveal sex-and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer\u2019s disease. Alzheimers Dement 19:518\u2013531","journal-title":"Alzheimers Dement"},{"key":"5978_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12859-019-2872-8","volume":"20","author":"H Yu","year":"2019","unstructured":"Yu H, Blair RH (2019) Integration of probabilistic regulatory networks into constraint-based models of metabolism with applications to Alzheimer\u2019s disease. BMC Bioinformatics 20:1\u201312","journal-title":"BMC Bioinformatics"},{"key":"5978_CR73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2009808118","volume":"118","author":"J Lord","year":"2021","unstructured":"Lord J, Jermy B, Green R, Wong A, Xu J, Legido-Quigley C, Dobson R, Richards M et al (2021) Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer\u2019s disease. Proc Natl Acad Sci 118:e2009808118","journal-title":"Proc Natl Acad Sci"},{"key":"5978_CR74","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ymben.2022.12.003","volume":"75","author":"S Gopalakrishnan","year":"2023","unstructured":"Gopalakrishnan S, Joshi CJ, Valderrama-G\u00f3mez M\u00c1, Icten E, Rolandi P, Johnson W, Kontoravdi C, Lewis NE (2023) Guidelines for extracting biologically relevant context-specific metabolic models using gene expression data. Metab Eng 75:181\u2013191","journal-title":"Metab Eng"},{"key":"5978_CR75","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.cels.2017.01.010","volume":"4","author":"S Opdam","year":"2017","unstructured":"Opdam S, Richelle A, Kellman B, Li S, Zielinski DC, Lewis NE (2017) A systematic evaluation of methods for tailoring genome-scale metabolic models. Cell Syst 4:318\u2013329","journal-title":"Cell Syst"},{"key":"5978_CR76","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.1016\/j.csbj.2021.06.009","volume":"19","author":"A Walakira","year":"2021","unstructured":"Walakira A, Rozman D, Re\u017een T, Mraz M, Mo\u0161kon M (2021) Guided extraction of genome-scale metabolic models for the integration and analysis of omics data. Comput Struct Biotechnol J 19:3521\u20133530","journal-title":"Comput Struct Biotechnol J"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05978-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-05978-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-05978-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:03:20Z","timestamp":1781798600000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-05978-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":76,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["5978"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-05978-7","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"15 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No ethical approval is required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"702"}}