{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:03:26Z","timestamp":1763129006119,"version":"3.45.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100013003","name":"Universit\u00e0 degli Studi di Cagliari","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013003","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) and dementia with Lewy bodies (DLB)\u00a0are neurodegenerative disorders with overlapping clinical features, making differential diagnosis challenging. The AQEE and GGEE peptides, derived from the proVGF neuroprotein, have emerged as potential cerebrospinal fluid (CSF) biomarkers for dementia. Indeed, we previously observed a reduction in AQEE-10 levels using selected reaction monitoring (SRM) and GGEE levels using enzyme-linked immunosorbent assay (ELISA) in a cohort of DLB patients compared to both controls and AD patients. To better investigate the diagnostic utility of these peptides, we analyzed CSF samples from both the original cohort and a newly recruited cohort. The new cohort (cohort 1) included patients, from Ulm University Hospital, with Parkinson\u2019s disease dementia (PDD) and DLB (combined as PDD\/DLB;\u00a0\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200918), and AD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919). The previously analyzed cohort (cohort 2), from the Amsterdam University Medical Center, included DLB (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200944), AD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920), and cognitively healthy controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200922). AQEE-10 levels were quantified by multiple reaction monitoring (MRM) in cohort 1 and by ELISA in both cohorts. GGEE levels were measured by ELISA in cohort 1 to corroborate and extend previous findings. MRM-based analysis revealed a significant reduction of AQEE-10 levels in DLB compared to both controls and AD (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05; ROC-AUC: 78% and 82%, respectively). This finding was confirmed by ELISA, for both AQEE-10 and GGEE peptide levels, along with a positive correlation between their concentrations. These results support AQEE-10 and GGEE as promising peptide biomarkers for distinguishing DLB from other dementia.\n                  <\/jats:p>","DOI":"10.1007\/s00415-025-13441-1","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:57:40Z","timestamp":1762268260000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["VGF AQEE- and GGEE-peptides differentiate between dementia types"],"prefix":"10.1007","volume":"272","author":[{"given":"B.","family":"Noli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Muqaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Gouda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AL.","family":"Manai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Nagl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Anderl-Straub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Werner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Otto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. E.","family":"Teunissen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Oeckl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-208X","authenticated-orcid":false,"given":"C.","family":"Cocco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"issue":"11","key":"13441_CR1","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1586\/ern.11.155","volume":"11","author":"S Karantzoulis","year":"2012","unstructured":"Karantzoulis S, Galvin JE (2012) Distinguishing Alzheimer\u2019s disease from other major forms of dementia. Expert Rev Neurother 11(11):1579\u20131591. https:\/\/doi.org\/10.1586\/ern.11.155","journal-title":"Expert Rev Neurother"},{"key":"13441_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-61779-310-3_1","volume":"789","author":"JP Burbach","year":"2011","unstructured":"Burbach JP (2011) What are neuropeptides? Methods Mol Biol 789:1\u201336. https:\/\/doi.org\/10.1007\/978-1-61779-310-3_1","journal-title":"Methods Mol Biol"},{"issue":"7","key":"13441_CR3","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/s1043-2760(96)00123-3","volume":"7","author":"GL Ferri","year":"1996","unstructured":"Ferri GL, Possenti R (1996) Vgf a neurotrophin-inducible gene expressed in neuroendocrine tissues. Trends Endocrinol Metab 7(7):233\u2013239. https:\/\/doi.org\/10.1016\/s1043-2760(96)00123-3","journal-title":"Trends Endocrinol Metab"},{"issue":"6","key":"13441_CR4","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1111\/j.1469-7580.2010.01309.x","volume":"217","author":"C Cocco","year":"2010","unstructured":"Cocco C, D\u2019Amato F, Noli B, Ledda A, Brancia C, Bongioanni P, Ferri GL (2010) Distribution of VGF peptides in the human cortex and their selective changes in Parkinson\u2019s and Alzheimer\u2019s diseases. J Anat 217(6):683\u2013693. https:\/\/doi.org\/10.1111\/j.1469-7580.2010.01309.x","journal-title":"J Anat"},{"issue":"4","key":"13441_CR5","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800105","volume":"13","author":"G Sathe","year":"2019","unstructured":"Sathe G, Na CH, Renuse S, Madugundu AK, Albert M, Moghekar A, Pandey A (2019) Quantitative proteomic profiling of cerebrospinal fluid to identify candidate biomarkers for Alzheimer\u2019s Disease. Proteomics Clin Appl 13(4):e1800105. https:\/\/doi.org\/10.1002\/prca.201800105","journal-title":"Proteomics Clin Appl"},{"issue":"8","key":"13441_CR6","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1002\/pmic.200300470","volume":"3","author":"O Carrette","year":"2003","unstructured":"Carrette O, Demalte I, Scherl A, Yalkinoglu O, Corthals G, Burkhard P, Hochstrasser DF, Sanchez JC (2003) A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer\u2019s disease. Proteomics 3(8):1486\u20131494. https:\/\/doi.org\/10.1002\/pmic.200300470","journal-title":"Proteomics"},{"issue":"19","key":"13441_CR7","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.3390\/ijms20194674","volume":"20","author":"I Van Steenoven","year":"2019","unstructured":"Van Steenoven I, Noli B, Cocco C, Ferri GL, Oeckl P, Otto M, Koel-Simmelink et al (2019) VGF peptides in cerebrospinal fluid of patients with dementia with lewy bodies. Int J Mol Sci 20(19):4674. https:\/\/doi.org\/10.3390\/ijms20194674","journal-title":"Int J Mol Sci"},{"issue":"1","key":"13441_CR8","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13024-020-00388-2","volume":"15","author":"I Van Steenoven","year":"2020","unstructured":"Van Steenoven I, Koel-Simmelink MJA, Vergouw LJM, Tijms BM, Piersma SR, Pham TV, Bridel C et al (2020) Identification of novel cerebrospinal fluid biomarker candidates for dementia with Lewy bodies: a proteomic approach. Mol Neurodegener 15(1):36. https:\/\/doi.org\/10.1186\/s13024-020-00388-2","journal-title":"Mol Neurodegener"},{"issue":"1","key":"13441_CR9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/cells10010038","volume":"10","author":"WA Boiten","year":"2020","unstructured":"Boiten WA, van Steenoven I, Xiao MF, Worley PF, Noli B, Cocco C, Ferri GL et al (2020) Pathologically decreased CSF levels of synaptic marker NPTX2 in DLB are correlated with levels of alpha-synuclein and VGF. Cells 10(1):38. https:\/\/doi.org\/10.3390\/cells10010038","journal-title":"Cells"},{"issue":"34","key":"13441_CR10","doi-asserted-by":"publisher","first-page":"10800","DOI":"10.1523\/JNEUROSCI.23-34-10800.2003","volume":"23","author":"J Alder","year":"2003","unstructured":"Alder J, Thakker-Varia S, Bangasser DA, Kuroiwa M, Plummer MR, Shors TJ, Black IB (2003) Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity. J Neurosci 23(34):10800\u201310808. https:\/\/doi.org\/10.1523\/JNEUROSCI.23-34-10800.2003","journal-title":"J Neurosci"},{"issue":"3","key":"13441_CR11","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.140","volume":"3","author":"Y Noda","year":"2015","unstructured":"Noda Y, Shimazawa M, Tanaka H, Tamura S, Inoue T, Tsuruma K, Hara H (2015) VGF and striatal cell damage in in vitro and in vivo models of Huntington\u2019s disease. Pharmacol Res Perspect 3(3):e00140. https:\/\/doi.org\/10.1002\/prp2.140","journal-title":"Pharmacol Res Perspect"},{"issue":"42","key":"13441_CR12","doi-asserted-by":"publisher","first-page":"13377","DOI":"10.1523\/JNEUROSCI.1127-09.2009","volume":"29","author":"MS Riedl","year":"2009","unstructured":"Riedl MS, Braun PD, Kitto KF, Roiko SA, Anderson LB, Honda CN, Fairbanks CA, Vulchanova L (2009) Proteomic analysis uncovers novel actions of the neurosecretory protein VGF in nociceptive processing. J Neurosci 29(42):13377\u201313388. https:\/\/doi.org\/10.1523\/JNEUROSCI.1127-09.2009","journal-title":"J Neurosci"},{"issue":"3","key":"13441_CR13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE et al (2011) The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement 7(3):263\u2013269. https:\/\/doi.org\/10.1016\/j.jalz.2011.03.005","journal-title":"Alzheimers Dement"},{"issue":"Pt 9","key":"13441_CR14","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1093\/brain\/awr179","volume":"134","author":"K Rascovsky","year":"2011","unstructured":"Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134(Pt 9):2456\u20132477. https:\/\/doi.org\/10.1093\/brain\/awr179","journal-title":"Brain"},{"issue":"12","key":"13441_CR15","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1212\/01.wnl.0000187889.17253.b1","volume":"65","author":"IG McKeith","year":"2005","unstructured":"McKeith IG, Dickson DW, Lowe J, Emre M, O\u2019Brien JT, Feldman H, Cummings J et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology 65(12):1863\u20131872. https:\/\/doi.org\/10.1212\/01.wnl.0000187889.17253.b1","journal-title":"Neurology"},{"issue":"12","key":"13441_CR16","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1002\/mds.21507","volume":"22","author":"M Emre","year":"2007","unstructured":"Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, Mizuno Y, Broe GA et al (2007) Clinical diagnostic criteria for dementia associated with Parkinson\u2019s disease. Mov Disord 22(12):1689\u20131707. https:\/\/doi.org\/10.1002\/mds.21507","journal-title":"Mov Disord"},{"issue":"12","key":"13441_CR17","doi-asserted-by":"publisher","first-page":"7516","DOI":"10.1007\/s00415-024-12694-6","volume":"271","author":"B Muqaku","year":"2024","unstructured":"Muqaku B, Anderl-Straub S, Werner L, Nagl M, Otto M, Teunissen CE, Oeckl P (2024) Contactin proteins in cerebrospinal fluid show different alterations in dementias. J Neurol 271(12):7516\u20137524. https:\/\/doi.org\/10.1007\/s00415-024-12694-6","journal-title":"J Neurol"},{"issue":"7","key":"13441_CR18","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1093\/bioinformatics\/btq054","volume":"26","author":"B MacLean","year":"2010","unstructured":"MacLean B, Tomazela DM, Shulman N, Chambers M, Finney GL, Frewen B, Kern R et al (2010) Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26(7):966\u2013968. https:\/\/doi.org\/10.1093\/bioinformatics\/btq054","journal-title":"Bioinformatics"},{"issue":"3\u20134","key":"13441_CR19","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1159\/000540673","volume":"83","author":"C Cocco","year":"2024","unstructured":"Cocco C, Noli B, Manconi B, Contini C, Manca E, Pisanu C, Meloni A et al (2024) Lower plasma levels of selective VGF (non-acronymic) peptides in bipolar disorder: comparative analysis reveals distinct patterns across mood disorders and healthy controls. Neuropsychobiology 83(3\u20134):160\u2013169. https:\/\/doi.org\/10.1159\/000540673","journal-title":"Neuropsychobiology"},{"issue":"16","key":"13441_CR20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI177692","volume":"18","author":"MS Woo","year":"2024","unstructured":"Woo MS, Bal LC, Winschel I, Manca E, Walkenhorst M, Sevgili B, Sonner JK et al (2024) The NR4A2\/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis. J Clin Invest 18(16):e177692. https:\/\/doi.org\/10.1172\/JCI177692","journal-title":"J Clin Invest"},{"key":"13441_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2025.102780","volume":"93","author":"B Noli","year":"2025","unstructured":"Noli B, Borghero G, Mascia MM, Hkir M, Puligheddu M, Cocco C (2025) NERP-1 modifications in amyotrophic lateral sclerosis. Tissue Cell 93:102780. https:\/\/doi.org\/10.1016\/j.tice.2025.102780","journal-title":"Tissue Cell"},{"issue":"4","key":"13441_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci15040329","volume":"15","author":"AL Manai","year":"2025","unstructured":"Manai AL, Caria P, Noli B, Contini C, Manconi B, Etzi F, Cocco C (2025) VGF and its derived peptides in amyotrophic lateral sclerosis. Brain Sci 15(4):329. https:\/\/doi.org\/10.3390\/brainsci15040329","journal-title":"Brain Sci"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13441-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-025-13441-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-025-13441-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:00:59Z","timestamp":1763128859000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-025-13441-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":22,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["13441"],"URL":"https:\/\/doi.org\/10.1007\/s00415-025-13441-1","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"type":"print","value":"0340-5354"},{"type":"electronic","value":"1432-1459"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"25 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"PO received research support from the Cure Alzheimer Fund, ALS Association (24-SGP-691, 23-PPG-674\u20132), ALS Finding a Cure, the Charcot Foundation, the DZNE Innovation-to-Application program, consulting fees from LifeArc and Fundamental Pharma and travel support from Biogen. CET has reseach contracts with Acumen, ADx Neurosciences, AC-Immune, Alamar, Aribio, Axon Neurosciences, Beckman-Coulter, BioConnect, Bioorchestra, Brainstorm Therapeutics,Celgene, Cognition Therapeutics, EIP Pharma, Eisai, Eli Lilly, Fujirebio, Grifols, Instant Nano Biosensors, Merck, Novo Nordisk, Olink, PeopleBio, Quanterix, Roche, Toyama, Vivoryon. She is editor in chief of Alzheimer Research and Therapy, and serves on editorial boards of Medidact Neurologie\/Springer, and Neurology: Neuroimmunology & Neuroinflammation. M.O. received research support from the German Federal Ministry of Education and Research (projects: FTLDc 01GI1007A), the EU Moodmarker programme (01EW2008), the ALS Association, the foundation of the state Baden-W\u00fcrttemberg (D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009), and the Thierry Latran Foundation and EU\u2010MIRIADE and the Roux-programme of the Martin Luther University Halle (Saale); M.O. received consulting fees from Biogen, Axon, Roche, and Grifols; and participates on the Biogen ATLAS trial board.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"745"}}