BloodBased Biomarkers in the QC Program Henrik Zetterberg

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 6 E 10 + 4 G 8 (mid domain MAbs) linked to magnetic beads MALDI-TOF MS for Aβ profiling Selected reaction monitoring (SRM) triple quad MS for quantification è Aβ profile in plasma is similar to that in CSF è Trend for a decrease in plasma Aβ 42/40 ratio in AD è Aβ 42 in plasma is a very minor peak / low abundant è Too small pilot cohort to evaluate clinical utility

Ovod – A&D, 2017

Nakamura – Nature, 2018

Plasma tau in Alzheimer’s disease AD dementia n= 54 Healthy controls n= 25 0. 0022 >400 plasma samples from: AD Controls 8. 80 pg/m. L 4. 43 pg/m. L Zetterberg et al. , 2012 Normal elderly (4 -7 years follow-up) Mild cognitive impairment AD dementia

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

Nf. L - ELISA vs. Simoa LLo. D = 0. 26 ng/L; LLo. Q = 1. 95 ng/L

Plasma Nf. L correlates with CSF Nf. L Gisslén et al. , 2015

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

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

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 , unpublished

Serum Nf. L in multiple sclerosis – before and after treatment with natalizumab Unpublished

Time to include blood-based biomarkers in the AA QC program? • Plasma Aβ 40 and Aβ 42? • Plasma/serum Nf. L?