{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T22:09:37Z","timestamp":1782166177640,"version":"3.54.5"},"reference-count":197,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating Alzheimer\u2032s Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.<\/jats:p>","DOI":"10.3390\/diagnostics12040796","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:05:18Z","timestamp":1648166718000},"page":"796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Fluid Biomarkers in Alzheimer\u2019s Disease and Other Neurodegenerative Disorders: Toward Integrative Diagnostic Frameworks and Tailored Treatments"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-2691","authenticated-orcid":false,"given":"Linda","family":"Giampietri","sequence":"first","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Belli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Beatino","sequence":"additional","affiliation":[{"name":"Psychiatry Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-0412","authenticated-orcid":false,"given":"Sara","family":"Giannoni","sequence":"additional","affiliation":[{"name":"Neurology Unit, Ospedale San Giuseppe, 50053 Empoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9193-3150","authenticated-orcid":false,"given":"Giovanni","family":"Palermo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Campese","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Tognoni","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Ceravolo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8146-5736","authenticated-orcid":false,"given":"Ciro","family":"De Luca","sequence":"additional","affiliation":[{"name":"Laboratory of Morphology of Neuronal Network and Systems Biology, Department of Mental and Physical Health and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-0556","authenticated-orcid":false,"given":"Filippo","family":"Baldacci","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"ref_1","unstructured":"(2021, June 22). Numbers of People with Dementia Worldwide: An Update to the Estimates in the World Alzheimer Report. Available online: https:\/\/www.alzint.org\/resource\/numbers-of-people-with-dementia-worldwide\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1080\/13543784.2017.1323868","article-title":"Why do trials for Alzheimer\u2019s disease drugs keep failing? A discontinued drug perspective for 2010\u20132015","volume":"26","author":"Mehta","year":"2017","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1474-4422(09)70299-6","article-title":"Hypothetical model of dynamic biomarkers of the Alzheimer\u2019s pathological cascade","volume":"9","author":"Jack","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1002\/mds.22242","article-title":"The prodromal phase of sporadic Parkinson\u2019s disease: Does it exist and if so how long is it?","volume":"23","author":"Hawkes","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1001\/jamaneurol.2017.4243","article-title":"When do a-Synucleinopathies start? An epidemiological timeline a review","volume":"75","author":"Savica","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1002\/jcb.24234","article-title":"Early pathogenesis in the adult-onset neurodegenerative disease amyotrophic lateral sclerosis","volume":"113","author":"Izaurieta","year":"2012","journal-title":"J. Cell. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1097\/NEN.0b013e31824b211b","article-title":"Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005\u20132010","volume":"71","author":"Beach","year":"2012","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1136\/jnnp-2017-316844","article-title":"Accuracy of clinical diagnosis of dementia with Lewy bodies: A systematic review and meta-analysis","volume":"89","author":"Rizzo","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","article-title":"The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Albert","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jalz.2011.03.003","article-title":"Toward defining the preclinical stages of Alzheimer\u2019s disease: Recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease","volume":"7","author":"Sperling","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1002\/mds.27802","article-title":"Update of the MDS research criteria for prodromal Parkinson\u2019s disease","volume":"34","author":"Heinzel","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/mds.26431","article-title":"MDS research criteria for prodromal Parkinson\u2019s disease","volume":"30","author":"Berg","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1212\/WNL.0000000000009323","article-title":"Research criteria for the diagnosis of prodromal dementia with Lewy bodies","volume":"94","author":"McKeith","year":"2020","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1080\/14737159.2020.1731306","article-title":"The path to biomarker-based diagnostic criteria for the spectrum of neurodegenerative diseases","volume":"20","author":"Baldacci","year":"2020","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00401-013-1157-y","article-title":"Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: A community-based autopsy series","volume":"126","author":"Kovacs","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1080\/14737175.2021.1965879","article-title":"Ultrasensitive techniques and protein misfolding amplification assays for biomarker-guided reconceptualization of Alzheimer\u2019s and other neurodegenerative diseases","volume":"21","author":"Campese","year":"2021","journal-title":"Expert Rev. Neurother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1093\/brain\/awy146","article-title":"Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated","volume":"141","author":"Robinson","year":"2018","journal-title":"Brain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14579","DOI":"10.1038\/s41598-020-71305-2","article-title":"Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer\u2019s disease neuropathology","volume":"10","author":"Thomas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","article-title":"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","volume":"7","author":"McKhann","year":"2011","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: The IWG-2 criteria","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1474-4422(20)30477-4","article-title":"Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease","volume":"20","author":"Hermann","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/ana.25334","article-title":"Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes","volume":"84","author":"Verberk","year":"2018","journal-title":"Ann. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.jalz.2019.03.009","article-title":"Plasma amyloid \u03b2 40\/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer\u2019s disease","volume":"15","author":"Vergallo","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"775","DOI":"10.3233\/JAD-190533","article-title":"Ultrasensitive Detection of Plasma Amyloid-\u03b2 as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer\u2019s Disease","volume":"71","author":"Chatterjee","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/brain\/awaa054","article-title":"Plasma tau, neurofilament light chain and amyloid-\u03b2 levels and risk of dementia; a population-based cohort study","volume":"143","author":"Ghanbari","year":"2020","journal-title":"Brain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jalz.2017.06.2266","article-title":"Amyloid \u03b2 concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis","volume":"13","author":"Ovod","year":"2017","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature25456","article-title":"High performance plasma amyloid-\u03b2 biomarkers for Alzheimer\u2019s disease","volume":"554","author":"Nakamura","year":"2018","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e8763","DOI":"10.15252\/emmm.201708763","article-title":"Amyloid blood biomarker detects Alzheimer\u2019s disease","volume":"10","author":"Nabers","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s13195-020-00738-8","article-title":"Amyloid-\u03b2 misfolding as a plasma biomarker indicates risk for future clinical Alzheimer\u2019s disease in individuals with subjective cognitive decline","volume":"12","author":"Stockmann","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1001\/jamaneurol.2017.1359","article-title":"Association of Plasma Total Tau Level With Cognitive Decline and Risk of Mild Cognitive Impairment or Dementia in the Mayo Clinic Study on Aging","volume":"74","author":"Mielke","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/brain\/awy347","article-title":"Plasma tau\/amyloid-\u03b21\u201342 ratio predicts brain tau deposition and neurodegeneration in Alzheimer\u2019s disease","volume":"142","author":"Park","year":"2019","journal-title":"Brain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jalz.2018.02.013","article-title":"Plasma phospho-tau181 increases with Alzheimer\u2019s disease clinical severity and is associated with tau- and amyloid-positron emission tomography","volume":"14","author":"Mielke","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jalz.2018.09.010","article-title":"Learnings about the complexity of extracellular tau aid development of a blood-based screen for Alzheimer\u2019s disease","volume":"15","author":"Chen","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41591-020-0755-1","article-title":"Plasma P-tau181 in Alzheimer\u2019s disease: Relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer\u2019s dementia","volume":"26","author":"Janelidze","year":"2020","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41591-020-0762-2","article-title":"Diagnostic value of plasma phosphorylated tau181 in Alzheimer\u2019s disease and frontotemporal lobar degeneration","volume":"26","author":"Thijssen","year":"2020","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S1474-4422(20)30071-5","article-title":"Blood phosphorylated tau 181 as a biomarker for Alzheimer\u2019s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts","volume":"19","author":"Karikari","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1038\/s41467-020-15436-0","article-title":"Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer\u2019s disease","volume":"11","author":"Janelidze","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1002\/alz.12236","article-title":"Head-to-head comparison of clinical performance of CSF phospho-tau T181 and T217 biomarkers for Alzheimer\u2019s disease diagnosis","volume":"17","author":"Karikari","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e20200861","DOI":"10.1084\/jem.20200861","article-title":"Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer\u2019s disease","volume":"217","author":"Horie","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1001\/jama.2020.12134","article-title":"Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders","volume":"324","author":"Palmqvist","year":"2020","journal-title":"JAMA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3233\/JAD-150167","article-title":"Greater Specificity for Cerebrospinal Fluid P-tau231 over P-tau181 in the Differentiation of Healthy Controls from Alzheimer\u2019s Disease","volume":"49","author":"Spiegel","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00401-021-02275-6","article-title":"Plasma p-tau231: A new biomarker for incipient Alzheimer\u2019s disease pathology","volume":"141","author":"Ashton","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1007\/s12035-020-02035-9","article-title":"Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases","volume":"57","author":"Palermo","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13195-018-0404-9","article-title":"Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer\u2019s disease","volume":"10","author":"Lewczuk","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1001\/jamaneurol.2019.0765","article-title":"Association between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients with Alzheimer Disease","volume":"76","author":"Mattsson","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neurobiolaging.2017.06.002","article-title":"Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer\u2019s disease","volume":"58","author":"Pereira","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.3233\/JAD-190615","article-title":"Neurofilament Light Chain in Cerebrospinal Fluid and Blood as a Biomarker for Neurodegenerative Diseases: A Systematic Review and Meta-Analysis","volume":"72","author":"Wang","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40478-018-0649-3","article-title":"Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration","volume":"7","author":"Ashton","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1001\/jamaneurol.2016.6117","article-title":"Association of Plasma Neurofilament Light With Neurodegeneration in Patients with Alzheimer Disease","volume":"74","author":"Mattsson","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6904","DOI":"10.18632\/aging.102220","article-title":"Neurofilament light chain plasma concentration predicts neurodegeneration and clinical progression in nondemented elderly adults","volume":"11","author":"Hu","year":"2019","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/s41591-018-0304-3","article-title":"Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer\u2019s disease","volume":"25","author":"Preische","year":"2019","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1212\/WNL.0000000000004667","article-title":"Serum neurofilament light in familial Alzheimer disease","volume":"89","author":"Weston","year":"2017","journal-title":"Neurology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/nan.12511","article-title":"Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with Amyotrophic Lateral Sclerosis","volume":"45","author":"Gille","year":"2019","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1212\/WNL.0000000000003688","article-title":"Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias","volume":"88","author":"Steinacker","year":"2017","journal-title":"Neurology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1001\/jamaneurol.2016.5398","article-title":"Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis","volume":"74","author":"Gaiani","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1136\/jnnp-2018-318704","article-title":"Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis","volume":"90","author":"Verde","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/ene.14063","article-title":"Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis","volume":"27","author":"Thouvenot","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1212\/WNL.0000000000004029","article-title":"Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease","volume":"88","author":"Poesen","year":"2017","journal-title":"Neurology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/ana.24552","article-title":"Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis","volume":"79","author":"Weydt","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jpsychires.2019.03.019","article-title":"Neurofilament light chain as a blood biomarker to differentiate psychiatric disorders from behavioural variant frontotemporal dementia","volume":"113","author":"Steinacker","year":"2019","journal-title":"J. Psychiatr. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s00415-019-09567-8","article-title":"Serum neurofilament light chain is a discriminative biomarker between frontotemporal lobar degeneration and primary psychiatric disorders","volume":"267","author":"Katisko","year":"2020","journal-title":"J. Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1212\/WNL.0000000000003680","article-title":"Blood-based NfL","volume":"88","author":"Hansson","year":"2017","journal-title":"Neurology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S1474-4422(19)30024-9","article-title":"CSF and blood biomarkers for Parkinson\u2019s disease","volume":"18","author":"Parnetti","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e1479","DOI":"10.1212\/WNL.0000000000007179","article-title":"Serum NFL discriminates Parkinson disease from atypical parkinsonisms","volume":"92","author":"Marques","year":"2019","journal-title":"Neurology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/ana.26089","article-title":"Alpha-Synuclein Oligomers and Neurofilament Light Chain Predict Phenoconversion of Pure Autonomic Failure","volume":"89","author":"Singer","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00401-018-1932-x","article-title":"Current state of Alzheimer\u2019s fluid biomarkers","volume":"136","author":"Molinuevo","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/14789450.2020.1831388","article-title":"The role of synaptic biomarkers in the spectrum of neurodegenerative diseases","volume":"17","author":"Mazzucchi","year":"2020","journal-title":"Expert Rev. Proteom."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.jalz.2014.10.009","article-title":"Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer\u2019s disease","volume":"11","author":"Kvartsberg","year":"2015","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1001\/jamaneurol.2015.1867","article-title":"Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease","volume":"72","author":"Kester","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1136\/jnnp-2018-320155","article-title":"CSF neurogranin as a neuronal damage marker in CJD: A comparative study with AD","volume":"90","author":"Blennow","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1001\/jamaneurol.2016.0086","article-title":"Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease","volume":"73","author":"Tarawneh","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.15252\/emmm.201606540","article-title":"Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer\u2019s disease","volume":"8","author":"Mattsson","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.3233\/JAD-170368","article-title":"Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study","volume":"59","author":"Lista","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/acn3.518","article-title":"CSF neurogranin or tau distinguish typical and atypical Alzheimer disease","volume":"5","author":"Wellington","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1093\/brain\/awv267","article-title":"Cerebrospinal fluid neurogranin: Relation to cognition and neurodegeneration in Alzheimer\u2019s disease","volume":"138","author":"Portelius","year":"2015","journal-title":"Brain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e887","DOI":"10.1212\/WNL.0000000000005057","article-title":"Neurogranin as a predictor of memory and executive function decline in MCI patients","volume":"90","author":"Headley","year":"2018","journal-title":"Neurology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.jalz.2019.01.004","article-title":"Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer\u2019s disease spectrum","volume":"15","author":"Bos","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e953","DOI":"10.1212\/WNL.0000000000010131","article-title":"Dissection of synaptic pathways through the CSF biomarkers for predicting Alzheimer disease","volume":"95","author":"Tible","year":"2020","journal-title":"Neurology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1750-1326-9-53","article-title":"SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer\u2019s disease","volume":"9","author":"Brinkmalm","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13195-018-0407-6","article-title":"Cerebrospinal fluid synaptosomal-associated protein 25 is a key player in synaptic degeneration in mild cognitive impairment and Alzheimer\u2019s disease","volume":"10","author":"Zhang","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.neuroscience.2018.11.038","article-title":"A Novel ELISA for the Measurement of Cerebrospinal Fluid SNAP-25 in Patients with Alzheimer\u2019s Disease","volume":"420","author":"Brinkmalm","year":"2019","journal-title":"Neuroscience"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13195-016-0208-8","article-title":"The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer\u2019s disease","volume":"8","author":"Brinkmalm","year":"2016","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Del Prete, E., Beatino, M.F., Campese, N., Giampietri, L., Siciliano, G., Ceravolo, R., and Baldacci, F. (2020). Fluid Candidate Biomarkers for Alzheimer\u2019s Disease: A Precision Medicine Approach. J. Pers. Med., 10.","DOI":"10.3390\/jpm10040221"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/14789450.2019.1628643","article-title":"The neuroinflammatory biomarker YKL-40 for neurodegenerative diseases: Advances in development","volume":"16","author":"Baldacci","year":"2019","journal-title":"Expert Rev. Proteom."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/14789450.2017.1304217","article-title":"Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer\u2019s disease and other neurodegenerative diseases","volume":"14","author":"Baldacci","year":"2017","journal-title":"Expert Rev. Proteom."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12974-017-0893-7","article-title":"YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer\u2019s disease and other tauopathies","volume":"14","author":"Pegueroles","year":"2017","journal-title":"J. Neuroinflam."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1212\/WNL.0000000000004088","article-title":"CSF sAPP\u03b2, YKL-40, and neurofilament light in frontotemporal lobar degeneration","volume":"89","author":"Alcolea","year":"2017","journal-title":"Neurology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1136\/jnnp-2018-318868","article-title":"Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase","volume":"90","author":"Oeckl","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1136\/jnnp-2017-317793","article-title":"Neurofilament light chain and tau concentrations are markedly increased in the serum of patients with sporadic Creutzfeldt-Jakob disease, and tau correlates with rate of disease progression","volume":"89","author":"Thompson","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_91","first-page":"53","article-title":"Development and validation of a salivary tau biomarker in Alzheimer\u2019s disease","volume":"10","author":"Pekeles","year":"2018","journal-title":"Alzheimer\u2019s Dement. Diagn. Assess. Dis. Monit."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.neulet.2018.12.030","article-title":"\u03b1-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson\u2019s disease","volume":"696","author":"Cao","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/mds.27328","article-title":"Evaluation of salivary heme oxygenase-1 as a potential biomarker of early Parkinson\u2019s disease","volume":"33","author":"Song","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/ana.21910","article-title":"Olfactory epithelium amyloid-\u03b2 and paired helical filament-tau pathology in Alzheimer disease","volume":"67","author":"Arnold","year":"2010","journal-title":"Ann. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JAD-122443","article-title":"Amyloid-\u03b2 Deposition and Olfactory Dysfunction in an Alzheimer\u2019s Disease Model","volume":"37","author":"Wu","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1007\/s00406-018-0955-6","article-title":"Evaluation of the methoxy-X04 derivative BSC4090 for diagnosis of prodromal and early Alzheimer\u2019s disease from bioptic olfactory mucosa","volume":"269","author":"Pellkofer","year":"2019","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40035-019-0164-x","article-title":"Efficient RT-QuIC seeding activity for \u03b1-synuclein in olfactory mucosa samples of patients with Parkinson\u2019s disease and multiple system atrophy","volume":"8","author":"Elia","year":"2019","journal-title":"Transl. Neurodegener."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"fcab045","DOI":"10.1093\/braincomms\/fcab045","article-title":"Alpha-synuclein seeds in olfactory mucosa and cerebrospinal fluid of patients with dementia with Lewy bodies","volume":"3","author":"Perra","year":"2021","journal-title":"Brain Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1093\/brain\/awab005","article-title":"Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder","volume":"144","author":"Stefani","year":"2021","journal-title":"Brain"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/mds.28399","article-title":"Immunohistochemical Detection of Synuclein Pathology in Skin in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinsonism","volume":"36","author":"Tsao","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00401-017-1684-z","article-title":"Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson\u2019s disease","volume":"133","author":"Doppler","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1001\/jamaneurol.2020.3311","article-title":"Skin \u03b1-Synuclein Aggregation Seeding Activity as a Novel Biomarker for Parkinson Disease","volume":"78","author":"Wang","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1159\/000505851","article-title":"A Pilot Study of Urinary Exosomes in Alzheimer\u2019s Disease","volume":"19","author":"Sun","year":"2019","journal-title":"Neurodegener. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Yilmaz, A., Ugur, Z., Bisgin, H., Akyol, S., Bahado-Singh, R., Wilson, G., Imam, K., Maddens, M.E., and Graham, S.F. (2020). Targeted Metabolic Profiling of Urine Highlights a Potential Biomarker Panel for the Diagnosis of Alzheimer\u2019s Disease and Mild Cognitive Impairment: A Pilot Study. Metabolites, 10.","DOI":"10.3390\/metabo10090357"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/19768354.2021.1883735","article-title":"Analysis of \u03b1-synuclein levels related to LRRK2 kinase activity: From substantia nigra to urine of patients with Parkinson\u2019s disease","volume":"25","author":"Nam","year":"2021","journal-title":"Animal Cells Syst."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1007\/s00415-020-10047-7","article-title":"Urinary neopterin, a new marker of the neuroinflammatory status in amyotrophic lateral sclerosis","volume":"267","author":"Lunetta","year":"2020","journal-title":"J. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neulet.2014.10.010","article-title":"Retinal neurodegeneration on optical coherence tomography and cerebral atrophy","volume":"584","author":"Ong","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s00401-016-1613-6","article-title":"Ocular indicators of Alzheimer\u2019s: Exploring disease in the retina","volume":"132","author":"Hart","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"921","DOI":"10.3389\/fnins.2020.00921","article-title":"Alzheimer\u2019s Retinopathy: Seeing Disease in the Eyes","volume":"14","author":"Mirzaei","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-021-00230-9","article-title":"Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer\u2019s disease","volume":"10","author":"Zhang","year":"2021","journal-title":"Transl. Neurodegener."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1001\/jamaophthalmol.2020.5730","article-title":"Characterization of Retinal Microvascular and Choroidal Structural Changes in Parkinson Disease","volume":"139","author":"Robbins","year":"2021","journal-title":"JAMA Ophthalmol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneurol.2016.65","article-title":"Advanced tests for early and accurate diagnosis of Creutzfeldt\u2013Jakob disease","volume":"12","author":"Zanusso","year":"2016","journal-title":"Nat. Rev. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3389\/fneur.2018.00415","article-title":"Are We Ready for Detecting \u03b1-Synuclein Prone to Aggregation in Patients? The Case of \u201cProtein-Misfolding Cyclic Amplification\u201d and \u201cReal-Time Quaking-Induced Conversion\u201d as Diagnostic Tools","volume":"9","author":"Paciotti","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40478-020-00990-x","article-title":"Towards an improved early diagnosis of neurodegenerative diseases: The emerging role of in vitro conversion assays for protein amyloids","volume":"8","author":"Candelise","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.cll.2020.04.002","article-title":"Proteopathic Seed Amplification Assays for Neurodegenerative Disorders","volume":"40","author":"Ferreira","year":"2020","journal-title":"Clin. Lab. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/B978-0-444-63945-5.00019-2","article-title":"Prion protein amplification techniques","volume":"153","author":"Green","year":"2018","journal-title":"Handb. Clin. Neurol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/bs.pmbts.2020.08.005","article-title":"Cell-free amplification of prions: Where do we stand?","volume":"175","author":"Cazzaniga","year":"2020","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/ana.25447","article-title":"\u03b1-Synuclein real-time quaking-induced conversion in the cerebrospinal fluid of uncertain cases of parkinsonism","volume":"85","author":"Green","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1002\/acn3.50897","article-title":"\u03b1-Synuclein RT-QuIC assay in cerebrospinal fluid of patients with dementia with Lewy bodies","volume":"6","author":"Bongianni","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-018-0508-2","article-title":"Rapid and ultra-sensitive quantitation of disease-associated \u03b1-synuclein seeds in brain and cerebrospinal fluid by \u03b1Syn RT-QuIC","volume":"6","author":"Groveman","year":"2018","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00401-020-02160-8","article-title":"Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies","volume":"140","author":"Rossi","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41586-020-1984-7","article-title":"Discriminating \u03b1-synuclein strains in Parkinson\u2019s disease and multiple system atrophy","volume":"578","author":"Shahnawaz","year":"2020","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1001\/jamaneurol.2016.4547","article-title":"Development of a Biochemical Diagnosis of Parkinson Disease by Detection of \u03b1-Synuclein Misfolded Aggregates in Cerebrospinal Fluid","volume":"74","author":"Shahnawaz","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ana.25824","article-title":"Alpha-Synuclein Oligomers and Neurofilament Light Chain in Spinal Fluid Differentiate Multiple System Atrophy from Lewy Body Synucleinopathies","volume":"88","author":"Singer","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.nbd.2017.07.018","article-title":"Distinct \u03b1-Synuclein strains and implications for heterogeneity among \u03b1-Synucleinopathies","volume":"109","author":"Peng","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/acn3.338","article-title":"Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies","volume":"3","author":"Fairfoul","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S1474-4422(20)30449-X","article-title":"Detection of \u03b1-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: A longitudinal observational study","volume":"20","author":"Iranzo","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1002\/acn3.772","article-title":"Alpha-synuclein RT-QuIC in cerebrospinal fluid of LRRK 2-linked Parkinson\u2019s disease","volume":"6","author":"Garrido","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s00401-017-1692-z","article-title":"Ultrasensitive and selective detection of 3-repeat tau seeding activity in Pick disease brain and cerebrospinal fluid","volume":"133","author":"Saijo","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00401-019-02080-2","article-title":"4-Repeat tau seeds and templating subtypes as brain and CSF biomarkers of frontotemporal lobar degeneration","volume":"139","author":"Saijo","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"fcaa142","DOI":"10.1093\/braincomms\/fcaa142","article-title":"TDP-43 real-time quaking induced conversion reaction optimization and detection of seeding activity in CSF of amyotrophic lateral sclerosis and frontotemporal dementia patients","volume":"2","author":"Tran","year":"2020","journal-title":"Brain Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.celrep.2014.02.031","article-title":"Detection of Misfolded A\u03b2 Oligomers for Sensitive Biochemical Diagnosis of Alzheimer\u2019s Disease","volume":"7","author":"Salvadores","year":"2014","journal-title":"Cell Rep."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Canevelli, M., Remoli, G., Bacigalupo, I., Valletta, M., Blasi, M.T., Sciancalepore, F., Bruno, G., Cesari, M., and Vanacore, N. (2020). Use of biomarkers in ongoing research protocols on alzheimer\u2019s disease. J. Pers. Med., 10.","DOI":"10.3390\/jpm10030068"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41582-018-0116-6","article-title":"A critical appraisal of amyloid-\u03b2-targeting therapies for Alzheimer disease","volume":"15","author":"Panza","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/13543776.2021.1832463","article-title":"Small-molecule BACE1 inhibitors: A patent literature review (2011 to 2020)","volume":"31","author":"Rombouts","year":"2021","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1016\/j.bbamem.2013.06.005","article-title":"\u03b3-Secretase inhibitors and modulators","volume":"1828","author":"Golde","year":"2013","journal-title":"Biochim. Biophys. Acta\u2014Biomembr."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13195-018-0340-8","article-title":"Safety, Tolerability and Immunogenicity of an Active Anti-A\u03b240 Vaccine (ABvac40) in Patients with Alzheimer\u2019s Disease: A Randomised, Double-Blind, Placebo-Controlled, Phase I Trial","volume":"10","author":"Lacosta","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e045720","DOI":"10.1002\/alz.045720","article-title":"Safety, tolerability and immunogenicity of an active anti-A\u03b240 vaccine (ABvac40) in patients with amnestic mild cognitive impairment (A-MCI) or very mild alzheimer\u2019s disease (VM-AD): A randomized, double-blind, placebo-controlled, phase II trial","volume":"16","author":"Molina","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_139","unstructured":"(2021, May 31). Safety and Immunogenicity of Repeated Doses of ABvac40 in Patients with A-MCI or Vm-AD, Available online: https:\/\/clinicaltrials.gov\/show\/NCT03461276."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13195-017-0318-y","article-title":"A phase III randomized trial of gantenerumab in prodromal Alzheimer\u2019s disease","volume":"9","author":"Ostrowitzki","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1586\/eci.11.93","article-title":"Solanezumab for the treatment of mild-to-moderate Alzheimers disease","volume":"8","author":"Imbimbo","year":"2012","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1312889","article-title":"Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer\u2019s Disease","volume":"370","author":"Doody","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1056\/NEJMoa1705971","article-title":"Trial of Solanezumab for Mild Dementia Due to Alzheimer\u2019s Disease","volume":"378","author":"Honig","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_144","unstructured":"(2021, May 31). Clinical Trial of Solanezumab for Older Individuals Who May Be at Risk for Memory Loss, Available online: https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT02008357."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3233\/JAD-140741","article-title":"The murine Version of BAN2401 (mAb158) selectively reduces amyloid-\u03b2 protofibrils in brain and cerebrospinal fluid of tg-ArcSwe Mice","volume":"43","author":"Tucker","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13195-021-00813-8","article-title":"A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer\u2019s disease with lecanemab, an anti-A\u03b2 protofibril antibody","volume":"13","author":"Swanson","year":"2021","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"6412","DOI":"10.1038\/s41598-018-24501-0","article-title":"Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-\u03b2","volume":"8","author":"Arndt","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e047259","DOI":"10.1002\/alz.047259","article-title":"EMERGE and ENGAGE topline results: Phase 3 studies of aducanumab in early Alzheimer\u2019s disease","volume":"16","author":"Haeberlein","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_149","unstructured":"(2021, June 21). Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or with a Type of Early Onset Alzheimer\u2019s Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU001, Available online: https:\/\/clinicaltrials.gov\/show\/NCT01760005."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e038028","DOI":"10.1002\/alz.038028","article-title":"Solanezumab in-depth outcomes","volume":"16","author":"Farlow","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"e038049","DOI":"10.1002\/alz.038049","article-title":"Gantenerumab in-depth outcomes","volume":"16","author":"Salloway","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2174\/1567205017666200304085513","article-title":"Learning from the Past: A Review of Clinical Trials Targeting Amyloid, Tau and Neuroinflammation in Alzheimer\u2019s Disease","volume":"17","author":"Zilli","year":"2020","journal-title":"Curr. Alzheimer Res."},{"key":"ref_153","unstructured":"(2021, June 14). AADvac1|ALZFORUM. Available online: https:\/\/www.alzforum.org\/therapeutics\/aadvac1."},{"key":"ref_154","unstructured":"(2021, June 14). Axon Announces Positive Results from Phase II ADAMANT Trial for AADvac1 in Alzheimer\u2019s Disease. Available online: https:\/\/www.axon-neuroscience.eu\/src\/pr\/6.pdf."},{"key":"ref_155","unstructured":"(2021, June 14). A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants with Early Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04445831."},{"key":"ref_156","unstructured":"(2021, June 15). N-Terminal Tau Antibodies Fade, Mid-Domain Ones Push to the Fore|ALZFORUM. Available online: https:\/\/www.alzforum.org\/news\/conference-coverage\/n-terminal-tau-antibodies-fade-mid-domain-ones-push-fore."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"P252","DOI":"10.1016\/j.jalz.2019.06.077","article-title":"P1-052: A Single Ascending Dose Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of The Anti-Phospho-Tau Antibody JNJ-63733657 In Healthy Subjects","volume":"15","author":"Galpern","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S1474-4422(02)00133-3","article-title":"The potential of anti-inflammatory drugs for the treatment of Alzheimer\u2019s disease","volume":"1","author":"Aisen","year":"2002","journal-title":"Lancet Neurol."},{"key":"ref_159","first-page":"CD011459","article-title":"Aspirin and other non-steroidal anti-inflammatory drugs for the prevention of dementia","volume":"4","author":"Jordan","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_160","first-page":"CD006378","article-title":"Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer\u2019s disease","volume":"2","author":"Jaturapatporn","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"De Luca, C., Colangelo, A.M., Virtuoso, A., Alberghina, L., and Papa, M. (2020). Neurons, glia, extracellular matrix and neurovascular unit: A systems biology approach to the complexity of synaptic plasticity in health and disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041539"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e20200785","DOI":"10.1084\/jem.20200785","article-title":"Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer\u2019s disease model","volume":"217","author":"Wang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3389\/fimmu.2020.00456","article-title":"A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer\u2019s Disease","volume":"11","author":"Hampel","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_164","unstructured":"(2021, June 21). A Phase 2 Study to Evaluate Efficacy and Safety of AL002 in Participants with Early Alzheimer\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04592874."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1080\/19420862.2015.1102813","article-title":"Generation and preclinical characterization of an antibody specific for SEMA4D","volume":"8","author":"Fisher","year":"2016","journal-title":"MAbs"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e043971","DOI":"10.1002\/alz.043971","article-title":"Evidence that semaphorin 4D is upregulated in neurons in Huntington\u2019s and Alzheimer\u2019s diseases: Effects of a SEMA4D blocking antibody on FDG-PET in a clinical trial, and treatment rationale for its use in AD","volume":"16","author":"Evans","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_167","unstructured":"(2021, June 20). Alzforum.com. Pepinemab|ALZFORUM. Available online: https:\/\/www.alzforum.org\/therapeutics\/pepinemab."},{"key":"ref_168","unstructured":"(2021, June 20). SEMA4D Blockade Safety and Brain Metabolic Activity in Alzheimer\u2019s Disease (AD), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04381468."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1007\/s00415-019-09363-4","article-title":"An update on genetic frontotemporal dementia","volume":"266","author":"Greaves","year":"2019","journal-title":"J. Neurol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"150","DOI":"10.3389\/fnins.2021.639078","article-title":"Moving toward Patient-Tailored Treatment in ALS and FTD: The Potential of Genomic Assessment as a Tool for Biological Discovery and Trial Recruitment","volume":"15","author":"Broce","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1093\/hmg\/ddl241","article-title":"Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration","volume":"15","author":"Gass","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1038\/s41598-017-02364-1","article-title":"Age-related penetrance of the C9orf72 repeat expansion","volume":"7","author":"Murphy","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41582-018-0009-8","article-title":"Genotype\u2013phenotype links in frontotemporal lobar degeneration","volume":"14","author":"Engelborghs","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1136\/jnnp-2018-320033","article-title":"Neurofilaments and tau in CSF in an infant with SMA type 1 treated with nusinersen","volume":"90","author":"Winter","year":"2019","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_175","unstructured":"(2021, June 22). Alector Announces Data from On-Going Phase 1b Trial Demonstrating That AL001 Reverses Progranulin Deficiency in Frontotemporal Dementia Patients. Available online: https:\/\/investors.alector.com\/news-releases\/news-release-details\/alector-announces-data-going-phase-1b-trial-demonstrating-al001."},{"key":"ref_176","unstructured":"(2021, June 22). A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04374136."},{"key":"ref_177","unstructured":"(2021, June 21). A Study of PBFT02 in Patients with Frontotemporal Dementia and Progranulin Mutations (FTD-GRN), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04747431."},{"key":"ref_178","unstructured":"(2021, June 22). Phase 1\/2 Clinical Trial of PR006 in Patients with Frontotemporal Dementia with Progranulin Mutations (FTD-GRN), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04408625."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/nature05016","article-title":"Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17","volume":"442","author":"Baker","year":"2006","journal-title":"Nature"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1021\/jm500065f","article-title":"Protein Kinase CK-1 Inhibitors As New Potential Drugs for Amyotrophic Lateral Sclerosis","volume":"57","author":"Salado","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"a024117","DOI":"10.1101\/cshperspect.a024117","article-title":"Clinical Spectrum of Amyotrophic Lateral Sclerosis (ALS)","volume":"7","author":"Grad","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nn.3584","article-title":"State of play in amyotrophic lateral sclerosis genetics","volume":"17","author":"Renton","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1016\/S0140-6736(17)31287-4","article-title":"Amyotrophic lateral sclerosis","volume":"390","author":"Hardiman","year":"2017","journal-title":"Lancet"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41582-020-00434-z","article-title":"Improving clinical trial outcomes in amyotrophic lateral sclerosis","volume":"17","author":"Kiernan","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_185","unstructured":"(2021, June 18). A Study of BIIB067 When Initiated in Clinically Presymptomatic Adults with a Confirmed Superoxide Dismutase 1 Mutation, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04856982."},{"key":"ref_186","unstructured":"(2021, June 19). Study to Assess the Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB078 Administered to Previously Treated Adults C9ORF72-Associated Amyotrophic Lateral Sclerosis (ALS), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04288856."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Chen, C., Ding, X., Akram, N., Xue, S., and Luo, S.-Z. (2019). Fused in Sarcoma: Properties, Self-Assembly and Correlation with Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081622"},{"key":"ref_188","unstructured":"(2021, June 19). A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants with Fused in Sarcoma Mutations (FUS-ALS), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04768972."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13195-017-0297-z","article-title":"Alzheimer\u2019s disease prevention: From risk factors to early intervention","volume":"9","author":"Gramunt","year":"2017","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_191","first-page":"1299","article-title":"Meta-analysis of modifiable risk factors for Alzheimer\u2019s disease","volume":"86","author":"Xu","year":"2015","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"101250","DOI":"10.1016\/j.smrv.2019.101250","article-title":"Obstructive sleep apnea, cognition and Alzheimer\u2019s disease: A systematic review integrating three decades of multidisciplinary research","volume":"50","author":"Bubu","year":"2020","journal-title":"Sleep Med. Rev."},{"key":"ref_193","first-page":"11","article-title":"Baseline subjective memory complaints associate with increased risk of incident dementia: The PREADVISE trial","volume":"2","author":"Abner","year":"2015","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41572-018-0016-5","article-title":"REM sleep behaviour disorder","volume":"4","author":"Dauvilliers","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jalz.2016.02.002","article-title":"Preclinical Alzheimer\u2019s disease: Definition, natural history, and diagnostic criteria","volume":"12","author":"Dubois","year":"2016","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Ursin, F., Timmermann, C., and Steger, F. (2021). Ethical Implications of Alzheimer\u2019s Disease Prediction in Asymptomatic Individuals through Artificial Intelligence. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030440"},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"De Luca, C., Virtuoso, A., Maggio, N., Izzo, S., Papa, M., and Colangelo, A.M. (2020). Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207554"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/4\/796\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:42:16Z","timestamp":1760136136000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/4\/796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,24]]},"references-count":197,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["diagnostics12040796"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12040796","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,24]]}}}