{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T13:15:21Z","timestamp":1778591721535,"version":"3.51.4"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["101042625"],"award-info":[{"award-number":["101042625"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e0 degli Studi di Modena e Reggio Emilia"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["GeroScience"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clinical implementation of neurofilament light chain (NfL), a biomarker of neurodegeneration, remains challenging due to absence of reliable cutoffs and influence of confounding factors, particularly age. We aimed to develop an age-adjusted, two-threshold classification framework to support clinical interpretation of NfL in the neurodegenerative dementia diagnosis. We retrospectively enrolled subjects with cognitive\/behavioral disturbances and cognitively unimpaired controls (CTR). Participants underwent a baseline diagnostic workup, including at least a neuropsychological assessment, blood test, CSF and serum NfL measurement, and MRI, and were followed up for 2\u00a0years. At follow-up, they were diagnosed with either a neurodegenerative dementia [Alzheimer\u2019s Disease (AD), Frontotemporal Dementia (FTD), or Lewy Body Dementia (LBD)] or a non-neurodegenerative condition [Other Etiology (OE)]. AD, FTD, and LBD were grouped as Neurodegenerative (NDG), while OE and CTR were grouped as Non-Neurodegenerative (non-NDG). Bayesian regression models assessed the effects of age, disease duration, renal function, and gender on NfL. A weighted support vector machine (SVM) with leave-one-out cross-validation defined age-adjusted cutoffs using a two-threshold strategy constraining sensitivity\u2009\u2265\u200985% and limiting the intermediate zone. We included 217 subjects (158 NDG, 59 non-NDG). Serum and CSF NfL levels were significantly higher in NDG. Age strongly increased NfL levels, particularly in serum where diagnostic separation declined beyond age 70. The SVM-based model applied to CSF NfL defined continuous, age-adjusted, two-threshold cutoffs, identifying low-risk, high-risk, and intermediate zones. The proposed framework for CSF NfL provides a clinically oriented decision-support tool to stratify the likelihood of underlying neurodegeneration and guide diagnostic workup in cognitive neurology settings, pending external validation.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02296-7","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:43:02Z","timestamp":1778589782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-adjusted neurofilament light chain cutoffs for diagnosing neurodegenerative dementia: a two-threshold machine learning approach"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-0181","authenticated-orcid":false,"given":"Chiara","family":"Gallingani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Maramotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Carbone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Vinceti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Cossutti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najara","family":"Iacovino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Ballotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Salemme","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Urbano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Bedin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Chiari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Zamboni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Tondelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"2296_CR1","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1136\/jnnp-2018-320106","volume":"90","author":"L Gaetani","year":"2019","unstructured":"Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90:870\u201381. https:\/\/doi.org\/10.1136\/jnnp-2018-320106.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2296_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411624","volume":"24","author":"S Coppens","year":"2023","unstructured":"Coppens S, Lehmann S, Hopley C, Hirtz C. Neurofilament-light, a promising biomarker: analytical, metrological and clinical challenges. Int J Mol Sci. 2023;24:11624. https:\/\/doi.org\/10.3390\/ijms241411624.","journal-title":"Int J Mol Sci"},{"key":"2296_CR3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjno-2021-000143","volume":"3","author":"J Alagaratnam","year":"2021","unstructured":"Alagaratnam J, von Widekind S, De Francesco D, Underwood J, Edison P, Winston A, et al. Correlation between CSF and blood neurofilament light chain protein: A systematic review and meta-analysis. BMJ Neurol Open. 2021;3:e000143. https:\/\/doi.org\/10.1136\/bmjno-2021-000143.","journal-title":"BMJ Neurol Open"},{"key":"2296_CR4","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.3390\/diagnostics14212408","volume":"14","author":"T Urbano","year":"2024","unstructured":"Urbano T, Maramotti R, Tondelli M, Gallingani C, Carbone C, Iacovino N, et al. Comparison of serum and cerebrospinal fluid neurofilament light chain concentrations measured by Ella\u2122 and Lumipulse\u2122 in patients with cognitive impairment. Diagnostics (Basel). 2024;14:2408. https:\/\/doi.org\/10.3390\/diagnostics14212408.","journal-title":"Diagnostics (Basel)"},{"key":"2296_CR5","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41582-024-00955-x","volume":"20","author":"M Khalil","year":"2024","unstructured":"Khalil M, Teunissen CE, Lehmann S, Otto M, Piehl F, Ziemssen T, et al. Neurofilaments as biomarkers in neurological disorders \u2014 towards clinical application. Nat Rev Neurol. 2024;20:269\u201387. https:\/\/doi.org\/10.1038\/s41582-024-00955-x.","journal-title":"Nat Rev Neurol"},{"key":"2296_CR6","doi-asserted-by":"publisher","first-page":"2508","DOI":"10.1002\/acn3.51234","volume":"7","author":"C Barro","year":"2020","unstructured":"Barro C, Chitnis T, Weiner HL. Blood neurofilament light: A critical review of its application to neurologic disease. Ann Clin Transl Neurol. 2020;7:2508\u201323. https:\/\/doi.org\/10.1002\/acn3.51234.","journal-title":"Ann Clin Transl Neurol"},{"key":"2296_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14612-6","volume":"11","author":"M Khalil","year":"2020","unstructured":"Khalil M, Pirpamer L, Hofer E, Voortman MM, Barro C, Leppert D, et al. Serum neurofilament light levels in normal aging and their association with morphologic brain changes. Nat Commun. 2020;11:812. https:\/\/doi.org\/10.1038\/s41467-020-14612-6.","journal-title":"Nat Commun"},{"key":"2296_CR8","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1001\/jamaneurol.2019.1534","volume":"76","author":"C Bridel","year":"2019","unstructured":"Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE, NFL Group. Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: A systematic review and meta-analysis. JAMA Neurology. 2019;76:1035\u201348. https:\/\/doi.org\/10.1001\/jamaneurol.2019.1534.","journal-title":"JAMA Neurology"},{"key":"2296_CR9","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1007\/s00415-023-12153-8","volume":"271","author":"J Sarto","year":"2024","unstructured":"Sarto J, Esteller-Gauxax D, Tort-Merino A, Guill\u00e9n N, P\u00e9rez-Millan A, Falg\u00e0s N, et al. Impact of demographics and comorbid conditions on plasma biomarkers concentrations and their diagnostic accuracy in a memory clinic cohort. J Neurol. 2024;271:1973\u201384. https:\/\/doi.org\/10.1007\/s00415-023-12153-8.","journal-title":"J Neurol"},{"key":"2296_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147808","volume":"25","author":"A Rodero-Romero","year":"2024","unstructured":"Rodero-Romero A, Monreal E, Sainz-Amo R, Garc\u00eda Dom\u00ednguez JM, Villarrubia N, Veiga-Gonz\u00e1lez JL, et al. Establishing normal serum values of neurofilament light chains and glial fibrillary acidic protein considering the effects of age and other demographic factors in healthy adults. Int J Mol Sci. 2024;25:7808. https:\/\/doi.org\/10.3390\/ijms25147808.","journal-title":"Int J Mol Sci"},{"key":"2296_CR11","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/ana.26446","volume":"92","author":"KC Fitzgerald","year":"2022","unstructured":"Fitzgerald KC, Sotirchos ES, Smith MD, Lord H-N, DuVal A, Mowry EM, et al. Contributors to serum NfL levels in people without neurologic disease. Ann Neurol. 2022;92:688\u201398. https:\/\/doi.org\/10.1002\/ana.26446.","journal-title":"Ann Neurol"},{"key":"2296_CR12","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1002\/alz.12177","volume":"17","author":"A Chiari","year":"2021","unstructured":"Chiari A, Vinceti G, Adani G, Tondelli M, Galli C, Fiondella L, et al. Epidemiology of early onset dementia and its clinical presentations in the province of Modena, Italy. Alzheimers Dement. 2021;17:81\u20138. https:\/\/doi.org\/10.1002\/alz.12177.","journal-title":"Alzheimers Dement"},{"key":"2296_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, Kawas CH, et al. 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. 2011;7:263\u20139. https:\/\/doi.org\/10.1016\/j.jalz.2011.03.005.","journal-title":"Alzheimers Dement"},{"key":"2296_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, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456\u201377. https:\/\/doi.org\/10.1093\/brain\/awr179.","journal-title":"Brain"},{"key":"2296_CR15","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1212\/WNL.0b013e31821103e6","volume":"76","author":"ML Gorno-Tempini","year":"2011","unstructured":"Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006\u201314. https:\/\/doi.org\/10.1212\/WNL.0b013e31821103e6.","journal-title":"Neurology"},{"key":"2296_CR16","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","volume":"89","author":"IG McKeith","year":"2017","unstructured":"McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor J-P, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89:88\u2013100. https:\/\/doi.org\/10.1212\/WNL.0000000000004058.","journal-title":"Neurology"},{"key":"2296_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jim.2017.08.009","volume":"451","author":"M Dysinger","year":"2017","unstructured":"Dysinger M, Marusov G, Fraser S. Quantitative analysis of four protein biomarkers: an automated microfluidic cartridge-based method and its comparison to colorimetric ELISA. J Immunol Methods. 2017;451:1\u201310. https:\/\/doi.org\/10.1016\/j.jim.2017.08.009.","journal-title":"J Immunol Methods"},{"key":"2296_CR18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075091","volume":"8","author":"J Gaiottino","year":"2013","unstructured":"Gaiottino J, Norgren N, Dobson R, Topping J, Nissim A, Malaspina A, et al. Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS ONE. 2013;8:e75091. https:\/\/doi.org\/10.1371\/journal.pone.0075091.","journal-title":"PLoS ONE"},{"key":"2296_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v080.i01","volume":"80","author":"P-C B\u00fcrkner","year":"2017","unstructured":"B\u00fcrkner P-C. Brms: an R package for Bayesian multilevel models using Stan. J Stat Softw. 2017;80:1\u201328. https:\/\/doi.org\/10.18637\/jss.v080.i01.","journal-title":"J Stat Softw"},{"key":"2296_CR20","doi-asserted-by":"publisher","unstructured":"Batuwita R, Palade V. Class imbalance learning methods for support vector machines. In: He H, Ma Y, editors. Imbalanced learning: foundations, algorithms, and applications. John Wiley & Sons; 2013. p. 83\u201399. https:\/\/doi.org\/10.1002\/9781118646106.ch5.","DOI":"10.1002\/9781118646106.ch5"},{"key":"2296_CR21","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/s43587-023-00471-5","volume":"3","author":"WS Brum","year":"2023","unstructured":"Brum WS, Cullen NC, Janelidze S, Ashton NJ, Zimmer ER, Therriault J, et al. A two-step workflow based on plasma p-tau217 to screen for amyloid \u03b2 positivity with further confirmatory testing only in uncertain cases. Nat Aging. 2023;3:1079\u201390. https:\/\/doi.org\/10.1038\/s43587-023-00471-5.","journal-title":"Nat Aging"},{"key":"2296_CR22","doi-asserted-by":"publisher","first-page":"6506","DOI":"10.1002\/alz.14140","volume":"20","author":"DJ Figdore","year":"2024","unstructured":"Figdore DJ, Griswold M, Bornhorst JA, Graff-Radford J, Ramanan VK, Vemuri P, et al. Optimizing cutpoints for clinical interpretation of brain amyloid status using plasma p-tau217 immunoassays. Alzheimers Dement. 2024;20:6506\u201316. https:\/\/doi.org\/10.1002\/alz.14140.","journal-title":"Alzheimers Dement"},{"key":"2296_CR23","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1093\/brain\/awaa018","volume":"143","author":"S Ducharme","year":"2020","unstructured":"Ducharme S, Dols A, Laforce R, Devenney E, Kumfor F, van den Stock J, et al. Recommendations to distinguish behavioural variant frontotemporal dementia from psychiatric disorders. Brain. 2020;143:1632\u201350. https:\/\/doi.org\/10.1093\/brain\/awaa018.","journal-title":"Brain"},{"key":"2296_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.120014","volume":"565","author":"G Musso","year":"2025","unstructured":"Musso G, Gabelli C, Puthenparampil M, Cosma C, Cagnin A, Gallo P, et al. Blood biomarkers for Alzheimer\u2019s disease with the Lumipulse automated platform: age-effect and clinical value interpretation. Clin Chim Acta. 2025;565:120014. https:\/\/doi.org\/10.1016\/j.cca.2024.120014.","journal-title":"Clin Chim Acta"},{"key":"2296_CR25","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/alz.12283","volume":"17","author":"J Simr\u00e9n","year":"2021","unstructured":"Simr\u00e9n J, Leuzy A, Karikari TK, Hye A, Benedet AL, Lantero\u2010Rodriguez J, et al. The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer\u2019s disease. Alzheimers Dement. 2021;17:1145\u201356. https:\/\/doi.org\/10.1002\/alz.12283.","journal-title":"Alzheimers Dement"},{"key":"2296_CR26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cca.2022.08.017","volume":"535","author":"JA Bornhorst","year":"2022","unstructured":"Bornhorst JA, Figdore D, Campbell MR, Pazdernik VK, Mielke MM, Petersen RC, et al. Plasma neurofilament light chain (NfL) reference interval determination in an age-stratified cognitively unimpaired cohort. Clin Chim Acta. 2022;535:153\u20136. https:\/\/doi.org\/10.1016\/j.cca.2022.08.017.","journal-title":"Clin Chim Acta"},{"key":"2296_CR27","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1080\/00365513.2020.1730434","volume":"80","author":"CVB Hviid","year":"2020","unstructured":"Hviid CVB, Knudsen CS, Parkner T. Reference interval and preanalytical properties of serum neurofilament light chain in Scandinavian adults. Scand J Clin Lab Invest. 2020;80:291\u20135. https:\/\/doi.org\/10.1080\/00365513.2020.1730434.","journal-title":"Scand J Clin Lab Invest"},{"key":"2296_CR28","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 2018;14:535\u201362. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018.","journal-title":"Alzheimers Dement"},{"key":"2296_CR29","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.dadm.2019.08.009","volume":"11","author":"LM Forgrave","year":"2019","unstructured":"Forgrave LM, Ma M, Best JR, DeMarco ML. The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer\u2019s disease, frontotemporal dementia, and amyotrophic lateral sclerosis: a systematic review and meta-analysis. Alzheimers Dement Amst. 2019;11:730\u201343. https:\/\/doi.org\/10.1016\/j.dadm.2019.08.009.","journal-title":"Alzheimers Dement Amst"},{"key":"2296_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23620-z","volume":"12","author":"NJ Ashton","year":"2021","unstructured":"Ashton NJ, Janelidze S, Al Khleifat A, Leuzy A, van der Ende EL, Karikari TK, et al. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021;12:3400. https:\/\/doi.org\/10.1038\/s41467-021-23620-z.","journal-title":"Nat Commun"},{"key":"2296_CR31","doi-asserted-by":"publisher","first-page":"1832","DOI":"10.1002\/acn3.51676","volume":"9","author":"L Vermunt","year":"2022","unstructured":"Vermunt L, Otte M, Verberk IMW, Killestein J, Lemstra AW, van der Flier WM, et al. Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface. Ann Clin Transl Neurol. 2022;9:1832\u20137. https:\/\/doi.org\/10.1002\/acn3.51676.","journal-title":"Ann Clin Transl Neurol"},{"key":"2296_CR32","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci14030272","volume":"14","author":"C Gallingani","year":"2024","unstructured":"Gallingani C, Carbone C, Tondelli M, Zamboni G. Neurofilaments light chain in neurodegenerative dementias: a review of imaging correlates. Brain Sci. 2024;14:272. https:\/\/doi.org\/10.3390\/brainsci14030272.","journal-title":"Brain Sci"},{"key":"2296_CR33","doi-asserted-by":"publisher","first-page":"6115","DOI":"10.1002\/alz.14088","volume":"20","author":"IMW Verberk","year":"2024","unstructured":"Verberk IMW, Jutte J, Kingma MY, Vigneswaran S, Gouda MMTEE, van Engelen M-P, et al. Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice. Alzheimers Dement. 2024;20:6115\u201332. https:\/\/doi.org\/10.1002\/alz.14088.","journal-title":"Alzheimers Dement"}],"container-title":["GeroScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02296-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11357-026-02296-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11357-026-02296-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:43:03Z","timestamp":1778589783000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11357-026-02296-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":33,"alternative-id":["2296"],"URL":"https:\/\/doi.org\/10.1007\/s11357-026-02296-7","relation":{},"ISSN":["2509-2723"],"issn-type":[{"value":"2509-2723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"29 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 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":"The study was conducted in accordance with the Declaration of Helsinki. Prior to sample collection, all participants had provided written informed consent for the storage of CSF and blood samples in the Modena Neurobiobank (ethics committee approval no. 26\/2017) and for their use for research purposes (ethics committee approval no. 372\/2021).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}