Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid status

R.B. Mofrad*, P. Scheltens, S. Kim, S.M. Kang, Y.C. Youn, S.S.A. An, J. Tomassen, B.N.M. van Berckel, P.J. Visser, W.M. van Der Flier, C.E. Teunissen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Objective: We assessed the performance of plasma amyloid oligomerization tendency (OA beta) as a marker for abnormal amyloid status. Additionally, we examined long-term storage effects on plasma OA beta.

Methods: We included 399 subjects regardless of clinical diagnosis from the Amsterdam Dementia Cohort and European Medical Information Framework for AD project (age, 63.8 +/- 6.6; 44% female). Amyloid status was determined by visual read on positron emission tomography (PET; n(abnormal) = 206). Plasma OA beta was measured using the multimer detection system (MDS). Long-term storage effects on MDS-OA beta were assessed using general linear models. Associations between plasma MDS-OA beta and A beta-PET status were assessed using logistic regression and receiver operating characteristics analyses. Correlations between plasma MDS-OAP and CSF biomarker levels were evaluated using Pearson correlation analyses.

Results: MDS-OA beta was higher in individuals with abnormal amyloid, and it identified abnormal A beta-PET with an area under the curve (AUC) of 0.74 (95% CI, 0.67-0.81), especially in samples with a storage duration < 4 years. Combining APOEe4 and age with plasma MDS-OA beta revealed an AUC of 81% for abnormal amyloid PET status (95% CI, 74-87%). Plasma MDS-OA beta correlated negatively with MMSE (r = - 0.29, p < .01) and CSF A beta 42 (r = - 0.20, p < 0.05) and positively with CSF Tau (r = 0.20, p = 0.01).

Conclusions: Plasma MDS-OA beta combined with APOEe4 and age accurately identifies brain amyloidosis in a large A beta-confirmed population. Using plasma MDS-OA beta as a screener reduced the costs and number of PET scans needed to screen for amyloidosis, which is relevant for clinical trials. Additionally, plasma MDS-OA beta levels appeared affected by long-term storage duration, which could be of interest for others measuring plasma A beta biomarkers.

Original languageEnglish
Article number133
Number of pages10
JournalAlzheimer's Research & Therapy
Volume13
Issue number1
DOIs
Publication statusPublished - 26 Jul 2021

Keywords

  • Blood-based biomarker
  • Plasma A beta oligomer
  • Amyloid status
  • Multimer detection system
  • Long-term storage
  • ALZHEIMERS-DISEASE
  • DIAGNOSTIC-CRITERIA
  • PROTEIN OLIGOMERS
  • DEMENTIA
  • BIOMARKER
  • PERFORMANCE
  • HYPOTHESIS
  • CONSENSUS
  • FLUID

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