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

Rosha Babapour Mofrad*, Philip Scheltens, SangYun Kim, Sungmin Kang, Young Chul Youn, Seong Soo A. An, Jori Tomassen, Bart N. M. van Berckel, Pieter Jelle Visser, Wiesje M. van der Flier, Charlotte E. Teunissen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: We assessed the performance of plasma amyloid oligomerization tendency (OAβ) as a marker for abnormal amyloid status. Additionally, we examined long-term storage effects on plasma OAβ. 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 OAβ was measured using the multimer detection system (MDS). Long-term storage effects on MDS-OAβ were assessed using general linear models. Associations between plasma MDS-OAβ and Aβ-PET status were assessed using logistic regression and receiver operating characteristics analyses. Correlations between plasma MDS-OAβ and CSF biomarker levels were evaluated using Pearson correlation analyses. Results: MDS-OAβ was higher in individuals with abnormal amyloid, and it identified abnormal Aβ-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-OAβ revealed an AUC of 81% for abnormal amyloid PET status (95% CI, 74–87%). Plasma MDS-OAβ correlated negatively with MMSE (r = − 0.29, p <.01) and CSF Aβ42 (r = − 0.20, p < 0.05) and positively with CSF Tau (r = 0.20, p = 0.01). Conclusions: Plasma MDS-OAβ combined with APOEe4 and age accurately identifies brain amyloidosis in a large Aβ-confirmed population. Using plasma MDS-OAβ 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-OAβ levels appeared affected by long-term storage duration, which could be of interest for others measuring plasma Aβ biomarkers.

Original languageEnglish
Article number133
JournalAlzheimer's Research and Therapy
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Dec 2021

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