Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum.
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ABSTRACT: 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.
SUBMITTER: Mila-Aloma M
PROVIDER: S-EPMC7586814 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum.
Milà-Alomà Marta M Salvadó Gemma G Gispert Juan Domingo JD Vilor-Tejedor Natalia N Grau-Rivera Oriol O Sala-Vila Aleix A Sánchez-Benavides Gonzalo G Arenaza-Urquijo Eider M EM Crous-Bou Marta M González-de-Echávarri José Maria JM Minguillon Carolina C Fauria Karine K Simon Maryline M Kollmorgen Gwendlyn G Zetterberg Henrik H Blennow Kaj K Suárez-Calvet Marc M Molinuevo José Luis JL
Alzheimer's & dementia : the journal of the Alzheimer's Association 20200623 10
<h4>Introduction</h4>The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood.<h4>Methods</h4>We used NeuroToolKit and Elecsys<sup>®</sup> 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.< ...[more]
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