Open AccessCerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease
Author(s) -
Palmqvist Sebastian,
Insel Philip S,
Stomrud Erik,
Janelidze Shorena,
Zetterberg Henrik,
Brix Britta,
Eichenlaub Udo,
Dage Jeffrey L,
Chai Xiyun,
Blennow Kaj,
Mattsson Niklas,
Hansson Oskar
Publication year - 2019
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201911170
Subject(s) - neurogranin , cerebrospinal fluid , neurodegeneration , biomarker , neuroinflammation , pathology , amyloid (mycology) , amyloid β , disease , alzheimer's disease , medicine , tau protein , chemistry , phosphorylation , biochemistry , protein kinase c
Failures in Alzheimer's disease ( AD ) drug trials highlight the need to further explore disease mechanisms and alterations of biomarkers during the development of AD . Using cross‐sectional data from 377 participants in the Bio FINDER study, we examined seven cerebrospinal fluid ( CSF ) and six plasma biomarkers in relation to β‐amyloid (Aβ) PET uptake to understand their evolution during AD . In CSF , Aβ42 changed first, closely followed by Aβ42/Aβ40, phosphorylated‐tau (P‐tau), and total‐tau (T‐tau). CSF neurogranin, YKL ‐40, and neurofilament light increased after the point of Aβ PET positivity. The findings were replicated using Aβ42, Aβ40, P‐tau, and T‐tau assays from five different manufacturers. Changes were seen approximately simultaneously for CSF and plasma biomarkers. Overall, plasma biomarkers had smaller dynamic ranges, except for CSF and plasma P‐tau which were similar. In conclusion, using state‐of‐the‐art biomarkers, we identified the first changes in Aβ, closely followed by soluble tau. Only after Aβ PET became abnormal, biomarkers of neuroinflammation, synaptic dysfunction, and neurodegeneration were altered. These findings lend in vivo support of the amyloid cascade hypotheses in humans.