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

2. Historically, plasma Aβ could show any result

3. 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

4. Ovod – A&D, 2017

5. Nakamura – Nature, 2018

6. 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 pg/mL
Controls pg/mL
Zetterberg et al., 2012

7. Plasma tau in ADNI
Mattsson et al., Neurology 2016

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

9. Plasma tau in ADNI

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

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

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

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

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Weston et al., unpublished

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Unpublished

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