Blood-Based Biomarkers in the QC Program?

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Presentation transcript:

Blood-Based Biomarkers in the QC Program? Henrik Zetterberg & Kaj Blennow University of Gothenburg

Historically, plasma Aβ could show any result

Pilot study on plasma β–amyloid using mass spectrometry Plasma treated with nonionic detergent (n-OGP) to reduce matrix effects - binding to plasma proteins IP using 6E10 + 4G8 (mid domain MAbs) linked to magnetic beads MALDI-TOF MS for Aβ profiling Selected reaction monitoring (SRM) triple quad MS for quantification Trend for a decrease in plasma Aβ42/40 ratio in AD Too small pilot cohort to evaluate clinical utility Aβ profile in plasma is similar to that in CSF Aβ42 in plasma is a very minor peak / low abundant

Ovod – A&D, 2017

Nakamura – Nature, 2018

Plasma tau in Alzheimer’s disease AD dementia n= 54 Healthy controls n= 25 >400 plasma samples from: Normal elderly (4-7 years follow-up) Mild cognitive impairment AD dementia 0.0022 AD 8.80 pg/mL Controls 4.43 pg/mL Zetterberg et al., 2012

Plasma tau in ADNI Mattsson et al., Neurology 2016

Plasma tau in Alzheimer’s disease – no correlation to CSF… Zetterberg et al., 2012

Plasma tau in ADNI

NfL - ELISA vs. Simoa LLoD = 0.26 ng/L; LLoQ = 1.95 ng/L

Plasma NfL correlates with CSF NfL Gisslén et al., 2015

Plasma NfL in familial Alzheimer’s disease Weston et al., Neurology 2017

Plasma NfL in familial Alzheimer’s disease Weston et al., Neurology 2017

Plasma NfL in familial Alzheimer’s disease – longitudinal data Weston et al., unpublished

Serum NfL in multiple sclerosis – before and after treatment with natalizumab Unpublished

Time to include blood-based biomarkers in the AA QC program? Plasma Aβ40 and Aβ42? Plasma/serum NfL?