Publication:
Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease.

dc.contributor.authorMoscoso, Alexis
dc.contributor.authorGrothe, Michel J
dc.contributor.authorAshton, Nicholas J
dc.contributor.authorKarikari, Thomas K
dc.contributor.authorLantero-Rodriguez, Juan
dc.contributor.authorSnellman, Anniina
dc.contributor.authorSuarez-Calvet, Marc
dc.contributor.authorBlennow, Kaj
dc.contributor.authorZetterberg, Henrik
dc.contributor.authorSchöll, Michael
dc.contributor.groupAlzheimer’s Disease Neuroimaging Initiative
dc.date.accessioned2023-02-09T10:39:29Z
dc.date.available2023-02-09T10:39:29Z
dc.date.issued2021
dc.description.abstractImportance Plasma phosphorylated tau at threonine 181 (p-tau181) has been proposed as an easily accessible biomarker for the detection of Alzheimer disease (AD) pathology , but its ability to monitor disease progression in AD remains unclear.Objective To study the potential of longitudinal plasma p-tau181 measures for assessing neurodegeneration progression and cognitive decline in AD in comparison to plasma neurofilament light chain (NfL), a disease -nonspecific marker of neuronal injury .Design, Setting, and Participants This longitudinal cohort study included data from the Alzheimer’s Disease Neuroimaging Initiative from February 1, 2007, to June 6, 2016. Follow-up blood sampling was performed for up to 8 years. Plasma p-tau181 measurements were performed in 2020. This was a multicentric observational study of 1113 participants, including cognitively unimpaired participants as well as patients with cognitive impairment ( mild cognitive impairment and AD dementia ). Participants were eligible for inclusion if they had available plasma p-tau181 and NfL measurements and at least 1 fluorine -18–labeled fluorodeoxyglucose (FDG) positron emission tomography ( PET ) or structural magnetic resonance imaging scan performed at the same study visit. Exclusion criteria included any significant neurologic disorder other than suspected AD; presence of infection , infarction , or multiple lacunes as detected by magnetic resonance imaging ; and any significant systemic condition that could lead to difficulty complying with the protocol.Exposures Plasma p-tau181 and NfL measured with single-molecule array technology .Main Outcomes and Measures Longitudinal imaging markers of neurodegeneration (FDG PET and structural magnetic resonance imaging ) and cognitive test scores (Preclinical Alzheimer Cognitive Composite and Alzheimer Disease Assessment Scale–Cognitive Subscale with 13 tasks). Data were analyzed from June 20 to August 15, 2020.Results Of the 1113 participants (mean [SD] age, 74.0 [7.6] years; 600 men [53.9%]; 992 non- Hispanic White participants [89.1%]), a total of 378 individuals (34.0%) were cognitively unimpaired (CU) and 735 participants (66.0%) were cognitively impaired (CImp). Of the CImp group, 537 (73.1%) had mild cognitive impairment , and 198 (26.9%) had AD dementia . Longitudinal changes of plasma p-tau181 were associated with cognitive decline (CU: r = –0.24, P < .001; CImp: r = 0.34, P < .001) and a prospective decrease in glucose metabolism (CU: r = –0.05, P = .48; CImp: r = –0.27, P < .001) and gray matter volume (CU: r = –0.19, P < .001; CImp: r = –0.31, P < .001) in highly AD-characteristic brain regions. These associations were restricted to amyloid -β–positive individuals. Both plasma p-tau181 and NfL were independently associated with cognition and neurodegeneration in brain regions typically affected in AD. However, NfL was also associated with neurodegeneration in brain regions exceeding this AD-typical spatial pattern in amyloid -β–negative participants. Mediation analyses found that approximately 25% to 45% of plasma p-tau181 outcomes on cognition measures were mediated by the neuroimaging -derived markers of neurodegeneration, suggesting links between plasma p-tau181 and cognition independent of these measures .Conclusions and Relevance Study findings suggest that plasma p-tau181 was an accessible and scalable marker for predicting and monitoring neurodegeneration and cognitive decline and was, unlike plasma NfL, AD specific. The study findings suggest implications for the use of plasma biomarkers as measures to monitor AD progression in clinical practice and treatment trials.
dc.description.versionSi
dc.identifier.citationMoscoso A, Grothe MJ, Ashton NJ, Karikari TK, Lantero Rodríguez J, Snellman A, et al. Longitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease. JAMA Neurol. 2021 Apr 1;78(4):396-406.
dc.identifier.doi10.1001/jamaneurol.2020.4986
dc.identifier.essn2168-6157
dc.identifier.pmcPMC7802009
dc.identifier.pmid33427873
dc.identifier.unpaywallURLhttps://jamanetwork.com/journals/jamaneurology/articlepdf/2774467/jamaneurology_moscoso_2021_oi_200097_1617209054.31608.pdf
dc.identifier.urihttp://hdl.handle.net/10668/16951
dc.issue.number4
dc.journal.titleJAMA neurology
dc.journal.titleabbreviationJAMA Neurol
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number396-406
dc.provenanceRealizada la curación de contenido 09/06/2025.
dc.publisherAmerican Medical Association
dc.pubmedtypeJournal Article
dc.pubmedtypeMulticenter Study
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.pubmedtypeResearch Support, U.S. Gov't, Non-P.H.S.
dc.relation.publisherversionhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2020.4986
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectNeurofilament Proteins
dc.subjectBiomarkers
dc.subjectAged
dc.subjectHumans
dc.subjectNeurodegenerative Diseases
dc.subject.decsDisfunción cognitiva
dc.subject.decsNeuroimagen
dc.subject.decsEnfermedad de alzheimer
dc.subject.decsPruebas neuropsicológicas
dc.subject.decsDiagnóstico
dc.subject.decsSustancia gris
dc.subject.meshAged, 80 and over
dc.subject.meshAlzheimer Disease
dc.subject.meshCohort Studies
dc.subject.meshFemale
dc.subject.meshLongitudinal Studies
dc.subject.meshMale
dc.subject.meshPhosphorylation
dc.subject.meshProspective Studies
dc.subject.meshtau Proteins
dc.titleLongitudinal Associations of Blood Phosphorylated Tau181 and Neurofilament Light Chain With Neurodegeneration in Alzheimer Disease.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number78
dspace.entity.typePublication

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