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

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; 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.

Promising Blood Biomarkers for Clinical Use in Alzheimer’s Disease: A Focused Update

“…Other than the ultrasensitive technique of the conventional ELISA that uses epitope-overlapping Aβ antibodies to capture and detect Aβ multimers after spiking the plasma samples, using synthetic Aβ42 to enhance the oligomerization of Aβ 27 28 29 was recently approved by the Korean National Evidence-based Healthcare Collaborating Agency as a supplementary diagnostic tool for AD (#HTA-2021-81, https://nhta.neca.re.kr/nhta/publication/nhtaU0601L.ecg ).…”

“… 44 An association of increased Aβ level with an AD diagnosis and amyloid PET positivity was also found when using an ELISA-based multimer detection system (MDS) that measures oligomerized Aβ. 27 28 29 This MDS utilizes the aggregation tendency of blood Aβ to measure multimeric Aβ levels. The distinctive assay principle of MDS is thought to produce the opposite result.…”

Is liquid biopsy mature enough for the diagnosis of Alzheimer’s disease?

“…Specific antibodies are used in MDS, and the level of OAβ can be obtained by using a spectrophotometer. As the OAβ test has the potential for distinguishing between AD patients and healthy controls, MDS would be a promising method for AD diagnosis, for example, AlphalLISA assay and the Blood TM OAβ test (PeopleBio Inc., South Korea) (Lee et al, 2020;Babapour Mofrad et al, 2021;Dominguez et al, 2022).…”

Prediction of amyloid PET positivity via machine learning algorithms trained with EDTA-based blood amyloid-β oligomerization data

“…Amyloid PET has been used as a standard biomarker for participant selection in many clinical trials. Mofrad et al demonstrated a sensitivity of 76% and specificity of 67% for predicting amyloid PET positivity by using plasma MDS-OAβ and this technique reduced the costs and number of PET scans needed to screen for amyloidosis [13]. In this study, we tested various machine learning models to predict amyloid PET positivity using In clinical AD prediction, MDS-OAβ has been validated and commercialized using heparinized plasma, and previous studies have used these samples [10].…”