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

• Published in: Alzheimer's research & therapy 2021-07, Vol.13 (1), p.1-133, Article 133
• Main Authors: Babapour Mofrad, Rosha, Scheltens, Philip, Kim, SangYun, Kang, Sungmin, Youn, Young Chul, An, Seong Soo A., Tomassen, Jori, van Berckel, Bart N. M., Visser, Pieter Jelle, van der Flier, Wiesje M., Teunissen, Charlotte E.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid status; Biobanks; Blood-based biomarker; Dementia; Hemoglobin; Laboratories; Long-term storage; Multimer detection system; Peptides; Plasma; Plasma Aβ oligomer; Reproducibility
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-021-00873-w

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; nabnormal = 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.