Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid status
Open Access
- 26 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Alzheimer's Research & Therapy
- Vol. 13 (1), 1-10
- https://doi.org/10.1186/s13195-021-00873-w
Abstract
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. 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. 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). 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.Keywords
This publication has 44 references indexed in Scilit:
- Amyloid β-protein oligomers and Alzheimer’s diseaseAlzheimer's Research & Therapy, 2013
- Plasma amyloid-β oligomers level is a biomarker for Alzheimer’s disease diagnosisBiochemical and Biophysical Research Communications, 2012
- Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementiaBrain, 2011
- A Specific Enzyme-Linked Immunosorbent Assay for Measuring β-Amyloid Protein Oligomers in Human Plasma and Brain Tissue of Patients With Alzheimer DiseaseArchives of Neurology, 2009
- Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptideNature Reviews Molecular Cell Biology, 2007
- Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 2005
- Long‐Term Storage of ProteinsCurrent Protocols in Protein Science, 2002
- Mild Cognitive ImpairmentArchives of Neurology, 1999
- Vascular dementiaNeurology, 1993