Blood Amyloid-β Oligomerization as a Biomarker of Alzheimer’s Disease: A Blinded Validation Study

Abstract

INTRODUCTION: Oligomeric amyloid ß (Aß) is one of the major contributors to the pathomechanism of AD; Aß oligomerization in plasma can be measured using a Multimer Detection System-Oligomeric Aß (MDS-OAß) after incubation with spiked synthetic Aß. METHODS: We evaluated the clinical sensitivity and specificity of the MDS-OAß values by inBlood TM OAß test using heparin-treated plasma samples from 52 AD patients in comparison with 52 community-based subjects with normal cognition (NC). The inclusion criterion was proposed by the NINCDS-ADRDA and additionally required for the least 6 months of follow-up from the initial clinical diagnosis in the course of AD. RESULTS: The MDS-OAβ values were 1.43 ± 0.30 ng/ml in AD and 0.45 ± 0.19 (p <0.001) in NC, respectively. Using a cutoff value of 0.78 ng/ml, the results revealed that 100% sensitivity 92.31% specificity. DISCUSSION: MDS-OAß to measure plasma Aβ oligomerization is a valuable blood-based biomarker for clinical diagnosis of AD, with high sensitivity and specificity.

Plasma Amyloid-β Oligomerization Tendency Predicts Amyloid PET Positivity

“…AD group (n=27) was differentiated from age-matched normal control group (n=144) with AUC of 0.896 (sensitivity 83.3%, speci city 90.0%) [5]. A recent validation study with AD (n=52) and normal control (n=52) con rmed the diagnostic accuracy with AUC value of 0.999 (sensitivity 100%, speci city 92.31%) [6]. The current study was completed in more heterogeneous population including individuals with AD, MCI, SCD, or other neurodegenerative diseases, and predictability on amyloid PET positivity was comparable (AUC 0.855).…”

“…All tests were completed in duplicate and the average was used. 0.78 ng/ml was established as the cut-off value in the previous validation study and the plasma OAβ concentration equal to, or higher than the cut-off value was de ned as MDS-OAβ positive [6]. MDS-OAβ tester was blinded to clinical information including demographics and diagnosis.…”

“…The technique was further modi ed by spiking synthetic Aβ into plasma prior to the antigen-antibody reaction to measure oligomerization tendency of plasma Aβ. It measures the dynamic change of plasma oligomeric Aβ concentration which is higher in AD patients compared to normal healthy controls [5,6]. In previous studies MDS-OAβ could differentiate AD from normal control group with high sensitivity and speci city [5,6].…”

Development of molecular tools for diagnosis of Alzheimer’s disease that are based on detection of amyloidogenic proteins

“…Recent work by Youn et al [ 77 ] reported further improvement of the AβO amplification technique. The analysis was conducted using commercially available kit (inBlood™ OAβ test), produced by People Bio Inc, Korea.…”

“…An “ideal” biomarker should be (1) able to detect a fundamental feature of AD neuropathology, (2) validated in neuropathologically confirmed AD cases, (3) precise (able to detect AD early in its course and distinguish it from other dementias), (4) reliable, (5) non-invasive, (6) simple to perform, (7) inexpensive. Appearance of polymeric forms of Aβ in CSF and blood is a unique feature of AD, and recent data reviewed above [ 73 , 77 ] indicate that analysis of AβO levels possesses a great potential for discriminating between AD and other types of neurodegenerative and neurological disorders with sufficient sensitivity and specificity. Use of blood plasma rather than CSF opens a possibility for non-invasive sampling of biological material.…”