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

• 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 beta-amyloid (A beta) PET uptake to understand their evolution during AD. In CSF, A beta 42 changed first, closely followed by A beta 42/A beta 40, phosphorylated-tau (P-tau), and total-tau (T-tau). CSF neurogranin, YKL-40, and neurofilament light increased after the point of A beta PET positivity. The findings were replicated using A beta 42, A beta 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 beta, closely followed by soluble tau. Only after A beta 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

Alzheimer disease

amyloid positron emission tomography

cerebrospinal

fluid biomarkers

plasma biomarkers

neurofilament light

cognitive decline

beta

tau

neurodegeneration

neurogranin

markers

protein

trial

Research & Experimental Medicine

cerebrospinal fluid biomarkers

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