Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum

Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid-β (Aβ)42, Aβ40, phosphorylated tau (p-tau), total tau (t-tau), n...

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Detalles Bibliográficos
Autores: Milà Alomà, Marta, Salvadó, Gemma, Gispert, Juan Domingo, Vilor Tejedor, Natàlia, 1988-, Grau, Oriol (Grau Rivera), Sala Vila, Aleix, Sánchez Benavides, Gonzalo, Arenaza Urquijo, Eider M., Crous-Bou, Marta, González de Echávarri, José Maria, Minguillón, Carolina, Fauria, Karine, Simon, Maryline, Kollmorgen, Gwendlyn, Zetterberg, Henrik, Blennow, Kaj, Suárez-Calvet, Marc, Molinuevo, José Luis, ALFA Study
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/45463
Acceso en línea:http://hdl.handle.net/10230/45463
http://dx.doi.org/10.1002/alz.12131
Access Level:acceso abierto
Palabra clave:Alzheimer&apos
s disease
Biomarker
Neurodegeneration
Neuroinflammation
Preclinical
Descripción
Sumario:Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys® immunoassays to measure cerebrospinal fluid (CSF) amyloid-β (Aβ)42, Aβ40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α-synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum. Results: CSF t-tau, p-tau, and neurogranin increase throughout aging only in Aβ-positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p-tau and p-tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p-tau; t-tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Discussion: Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.

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