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

Marta Milà‐Alomà, Gemma Salvadó, Juan Domingo Gispert, Natalia Vilor‐Tejedor, Oriol Grau‐Rivera, Aleix Sala‐Vila, Gonzalo Sánchez‐Benavides, Eider M. Arenaza‐Urquijo, Marta Crous‐Bou, José Maria González‐de‐Echávarri, Carolina Minguillon, Karine Fauria (+7 others)
2020 Alzheimer's & Dementia  
The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. 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. CSF t-tau, p-tau, and neurogranin increase
more » ... granin 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. Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum.
doi:10.1002/alz.12131 pmid:32573951 fatcat:hclihedpovevfd7lxv27uj7xiq