{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:09:15Z","timestamp":1785251355272,"version":"3.55.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,1,5]]},"abstract":"<jats:p>Background: Plasma NfL (pNfL) levels are elevated in many neurological disorders. However, the utility of pNfL in a clinical setting has not been established. Objective: In a cohort of diverse older participants, we examined: 1) the association of pNfL to age, sex, Hispanic ethnicity, diagnosis, and structural and amyloid imaging biomarkers; and 2) its association to baseline and longitudinal cognitive and functional performance. Methods: 309 subjects were classified at baseline as cognitively normal (CN) or with cognitive impairment. Most subjects had structural MRI and amyloid PET scans. The most frequent etiological diagnosis was Alzheimer\u2019s disease (AD), but other neurological and neuropsychiatric disorders were also represented. We assessed the relationship of pNfL to cognitive and functional status, primary etiology, imaging biomarkers, and to cognitive and functional decline. Results: pNfL increased with age, degree of hippocampal atrophy, and amyloid load, and was higher in females among CN subjects, but was not associated with Hispanic ethnicity. Compared to CN subjects, pNfL was elevated among those with AD or FTLD, but not those with neuropsychiatric or other disorders. Hippocampal atrophy, amyloid positivity and higher pNfL levels each added unique variance in predicting greater functional impairment on the CDR-SB at baseline. Higher baseline pNfL levels also predicted greater cognitive and functional decline after accounting for hippocampal atrophy and memory scores at baseline. Conclusion: pNfL may have a complementary and supportive role to brain imaging and cognitive testing in a memory disorder evaluation, although its diagnostic sensitivity and specificity as a stand-alone measure is modest. In the absence of expensive neuroimaging tests, pNfL could be used for differentiating neurodegenerative disease from neuropsychiatric disorders.<\/jats:p>","DOI":"10.3233\/jad-200901","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T12:34:58Z","timestamp":1605616498000},"page":"59-70","source":"Crossref","is-referenced-by-count":21,"title":["Utility of Plasma Neurofilament Light in the 1Florida Alzheimer\u2019s Disease Research Center (ADRC)"],"prefix":"10.1177","volume":"79","author":[{"given":"Warren","family":"Barker","sequence":"first","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Quinonez","sequence":"additional","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T.","family":"Greig","sequence":"additional","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Behar","sequence":"additional","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Chirinos","sequence":"additional","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie A.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Rosselli","sequence":"additional","affiliation":[{"name":"Florida Atlantic University, Department of Psychology, Charles E. Schmidt College of Science, Davie, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam J.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Albizu University, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie Curiel","family":"Cid","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences and Neurology, Miller School of Medicine, University of Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Rundek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"McFarland","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Hanson","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Smith","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"DeKosky","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vaillancourt","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Adjouadi","sequence":"additional","affiliation":[{"name":"College of Engineering and Computing, Florida International University, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Marsiske","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufer","family":"Ertekin-Taner","sequence":"additional","affiliation":[{"name":"Mayo Clinic Florida, Department of Neuroscience, Jacksonville, FL, USA"},{"name":"Mayo Clinic Florida, Department of Neurology, Jacksonville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Golde","sequence":"additional","affiliation":[{"name":"Florida ADRC, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Loewenstein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences and Neurology, Miller School of Medicine, University of Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjan","family":"Duara","sequence":"additional","affiliation":[{"name":"Wien Center for Alzheimer\u2019s Disease and Memory Disorder, Mount Sinai Medical Center, Miami Beach, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-200901_ref1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/ana.25123","article-title":"Person-specific contribution of neuropathologies to cognitive loss in old age","volume":"83","author":"Boyle","year":"2018","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-200901_ref2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/jnr.1242","article-title":"Neurofilament protein in cerebrospinal fluid: A marker of white matter changes","volume":"66","author":"Sjogren","year":"2001","journal-title":"J Neurosci Res"},{"key":"10.3233\/JAD-200901_ref3","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1001\/jamaneurol.2015.3037","article-title":"Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression","volume":"73","author":"Zetterberg","year":"2016","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-200901_ref4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neurobiolaging.2016.09.012","article-title":"CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults","volume":"49","author":"Idland","year":"2017","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-200901_ref5","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":"10.3233\/JAD-200901_ref6","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.dadm.2019.08.008","article-title":"Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition.","volume":"11","author":"Osborn","year":"2019","journal-title":"Alzheimers Dement (Amst),"},{"key":"10.3233\/JAD-200901_ref7","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1001\/jamaneurol.2019.1534","article-title":"Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: A systematic review and meta-analysis","volume":"76","author":"Bridel","year":"2019","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-200901_ref8","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1097\/JGP.0b013e3182107c69","article-title":"Pre-MCI and MCI: Neuropsychological, clinical, and imaging features and progression rates","volume":"19","author":"Duara","year":"2011","journal-title":"Am J Geriatr Psychiatry"},{"key":"10.3233\/JAD-200901_ref9","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jalz.2011.03.002","article-title":"An investigation of PreMCI: Subtypes and longitudinal outcomes","volume":"8","author":"Loewenstein","year":"2012","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-200901_ref10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/WAD.0000000000000279","article-title":"Version 3 of the National Alzheimer\u2019s Coordinating Center\u2019s Uniform Data Set","volume":"32","author":"Besser","year":"2018","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"10.3233\/JAD-200901_ref11","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1212\/WNL.43.11.2412-a","article-title":"The Clinical Dementia Rating (CDR): Current version and scoring rules","volume":"43","author":"Morris","year":"1993","journal-title":"Neurology"},{"key":"10.3233\/JAD-200901_ref12","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/archneurol.2010.115","article-title":"Validation of the new interpretive guidelines for the clinical dementia rating scale sum of boxes score in the national Alzheimer\u2019s coordinating center database","volume":"67","author":"O\u2019Bryant","year":"2010","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-200901_ref13","unstructured":"National Research Council (2004) Measuring Racial Discrimination. The National Academies Press, Washington, DC."},{"key":"10.3233\/JAD-200901_ref14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1076\/clin.12.1.43.1726","article-title":"Hopkins verbal learning test\u2013revised: Normative data and analysis of inter-form and test-retest reliability","volume":"12","author":"Benedict","year":"1998","journal-title":"Clin Neuropsychol"},{"key":"10.3233\/JAD-200901_ref15","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state: A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"10.3233\/JAD-200901_ref16","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":"Alzheimers Dement"},{"key":"10.3233\/JAD-200901_ref17","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1212\/01.wnl.0000336925.79704.9f","article-title":"Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease","volume":"71","author":"Duara","year":"2008","journal-title":"Neurology"},{"key":"10.3233\/JAD-200901_ref18","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1093\/brain\/awp123","article-title":"Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer\u2019s disease","volume":"132","author":"Desikan","year":"2009","journal-title":"Brain"},{"key":"10.3233\/JAD-200901_ref19","doi-asserted-by":"crossref","first-page":"101800","DOI":"10.1016\/j.nicl.2019.101800","article-title":"Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity","volume":"22","author":"Duara","year":"2019","journal-title":"Neuroimage Clin"},{"key":"10.3233\/JAD-200901_ref20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s40336-015-0102-6","article-title":"Beta-amyloid imaging with florbetaben","volume":"3","author":"Sabri","year":"2015","journal-title":"Clin Transl Imaging"},{"key":"10.3233\/JAD-200901_ref21","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1007\/s00259-017-3749-6","article-title":"18F-Florbetaben PET beta-amyloid binding expressed in Centiloids","volume":"44","author":"Rowe","year":"2017","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"10.3233\/JAD-200901_ref22","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/j.jalz.2018.06.1353","article-title":"Standardization of amyloid quantitation with florbetapir standardized uptake value ratios to the Centiloid scale","volume":"14","author":"Navitsky","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-200901_ref23","doi-asserted-by":"crossref","first-page":"929","DOI":"10.2147\/NDT.S62323","article-title":"Disease progression model for Clinical Dementia Rating-Sum of Boxes in mild cognitive impairment and Alzheimer\u2019s subjects from the Alzheimer\u2019s Disease Neuroimaging Initiative","volume":"10","author":"Samtani","year":"2014","journal-title":"Neuropsychiatr Dis Treat"},{"key":"10.3233\/JAD-200901_ref24","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1017\/S104161020400033X","article-title":"Apolipoprotein E polymorphism and age of onset for Alzheimer\u2019s disease in a bi-ethnic sample","volume":"16","author":"Harwood","year":"2004","journal-title":"Int Psychogeriatr"},{"key":"10.3233\/JAD-200901_ref25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fnagi.2018.00193","article-title":"Amyloid-\u03b2, tau, and cognition in cognitively normal older individuals: Examining the necessity to adjust for biomarker status in normative data","volume":"10","author":"Bos","year":"2018","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-200901_ref26","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":"de Wolf","year":"2020","journal-title":"Brain"},{"key":"10.3233\/JAD-200901_ref27","doi-asserted-by":"crossref","unstructured":"Altomare D , de Wilde A , Ossenkoppele R , Pelkmans W , Bouwman F , Groot C , van Maurik I , Zwan M , Yaqub M , Barkhof F , van Berckel BN , Teunissen CE , Frisoni GB , Scheltens P , van der Flier WM (2019) Applying the ATN scheme in a memory clinic population: The ABIDE project.e1635-e1646. Neurology 93.","DOI":"10.1212\/WNL.0000000000008361"},{"key":"10.3233\/JAD-200901_ref28","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1001\/jama.2019.7437","article-title":"Associations of amyloid, tau, and neurodegeneration biomarker profiles with rates of memory decline among individuals without dementia","volume":"321","author":"Jack","year":"2019","journal-title":"JAMA"},{"key":"10.3233\/JAD-200901_ref29","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":"Alzheimers Dement"},{"key":"10.3233\/JAD-200901_ref30","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1212\/01.wnl.0000172914.08967.dc","article-title":"Aggregation of vascular risk factors and risk of incident Alzheimer disease","volume":"65","author":"Luchsinger","year":"2005","journal-title":"Neurology"},{"key":"10.3233\/JAD-200901_ref31","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1093\/brain\/awz099","article-title":"Limbic-predominant age-related TDP-43 encephalopathy (LATE): Consensus working group report","volume":"142","author":"Nelson","year":"2019","journal-title":"Brain"},{"key":"10.3233\/JAD-200901_ref32","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00401-014-1349-0","article-title":"Primary age-related tauopathy (PART): A common pathology associated with human aging","volume":"128","author":"Crary","year":"2014","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-200901_ref33","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/S1474-4422(12)70191-6","article-title":"Cognitive reserve in ageing and Alzheimer\u2019s disease","volume":"11","author":"Stern","year":"2012","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-200901_ref34","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1186\/s12974-018-1313-3","article-title":"Inflammation: The link between comorbidities, genetics, and Alzheimer\u2019s disease","volume":"15","author":"Newcombe","year":"2018","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JAD-200901_ref35","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"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-200901","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:04:31Z","timestamp":1777370671000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-200901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,5]]},"references-count":35,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jad-200901","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,5]]}}}