Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease.

ABSTRACT: 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 BioFINDER study, we examined seven cerebrospinal fluid (CSF) and six plasma biomarkers in relation to ?-amyloid (A?) PET uptake to understand their evolution during AD. In CSF, A?42 changed first, closely followed by A?42/A?40, phosphorylated-tau (P-tau), and total-tau (T-tau). CSF neurogranin, YKL-40, and neurofilament light increased after the point of A? PET positivity. The findings were replicated using A?42, A?40, 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 A?, closely followed by soluble tau. Only after A? 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.

SUBMITTER: Palmqvist S 

PROVIDER: S-EPMC6895602 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature