Premium
Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
Author(s) -
MilàAlomà Marta,
Salvadó Gemma,
Gispert Juan Domingo,
VilorTejedor Natalia,
GrauRivera Oriol,
SalaVila Aleix,
SánchezBenavides Gonzalo,
ArenazaUrquijo Eider M.,
CrousBou Marta,
GonzálezdeEchávarri José Maria,
Minguillon Carolina,
Fauria Karine,
Simon Maryline,
Kollmorgen Gwendlyn,
Zetterberg Henrik,
Blennow Kaj,
SuárezCalvet Marc,
Molinuevo José Luis
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12131
Subject(s) - neurogranin , neurodegeneration , cerebrospinal fluid , neuroscience , biomarker , tau protein , alzheimer's disease , amyloid beta , psychology , medicine , pathology , oncology , disease , chemistry , phosphorylation , biochemistry , protein kinase c
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 .