2020-06-23
Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
Publication
Publication
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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| doi.org/10.1002/alz.12131, hdl.handle.net/1765/128201 | |
| Alzheimer's & Dementia | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Milà-Alomà, M. (Marta), Salvadó, G. (Gemma), Gispert, J.D. (Juan Domingo), Vilor-Tejedor, N., Grau-Rivera, O., Sala-Vila, A. (Aleix), … Molinuevo, J.L. (José Luis). (2020). Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum. Alzheimer's & Dementia. doi:10.1002/alz.12131 |
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