Many researchers have chosen Aβ oligomers as a biomarker for the diagnosis of AD as it satisfies the criteria of an ideal biomarker, which was proposed by the Ronald and Nancy Reagan Research Institute-NIA in 1998 (25). Several studies have substantiated the positive correlation between the levels of Aβ oligomers in plasma and the likelihood of AD (26), and found the sensitivity and specificity to be less than 85% (6). The MDS-OAβ measures oligomerization dynamics of Aβ in the blood without the need for specialized equipment, unlike conventional techniques which directly measure Aβ molecules using larger machines due to the low concentration of target molecules in the blood (14). In this study, the oligomerization tendencies of Aβ in AD and normal plasma were measured using the MDS-OAβ, and we demonstrated that the sensitivity and specificity were 100% and 92.3%, respectively; therefore MDS-OAβ has very high sensitivity and specificity in distinguishing AD from NC. We used a stringent patient recruitment criterion for this study. For example, AD patients were followed-up for at least 6 months by experienced neurologists to rule out the possibility of cognitive impairment caused by any other disease, and community-based NC subjects without cognitive decline, were enrolled.
Although the data was not shown in this study, while assessing 29 cases of the AD, all patients showed high MDS-OAβ levels, and a PIB or Florbetaben PET was conducted. The standardized uptake value radio (SUVR) of 25 cases were positive, and 3 cases had a positive visual rating but negative SUVR. One case had a negative amyloid PET but had a typical CSF profile of AD. This patient may have a soluble form Aβ, which failed to produce Aβ plaques in the brain; therefore, only showing changes in the CSF biomarker (27–30). While the MDS-OAβ measures dynamics of Aβ oligomerization (14), amyloid PET only reveals the fibrillar form of Aβ in the brain (31), which may have caused the discrepancy. The other possible reason is that changes in CSF biomarkers may have occurred before the amyloid PET change. Aβ oligomerization tendency in plasma may reflect as early as changes in the CSF biomarker, and signify AD regardless of the solubility of Aβ.
Many studies have argued that biomarkers, such as brain volume and CSF Aβ42, p-tau, and t-tau which indicates the downstream effects of AD, show an increase in severity as the disease progress and formed a graph of the sigmoid curve (32, 33). However, the average of MDS-OAβ level in this study was the highest at CDR score 0.5 and the lower as AD progress (Fig. 3). MDS-OAβ measures the oligomerization dynamics of Aβ, which corresponds to the derivative of the sigmoid function of Aβ accumulation. It is possible that this biomarker changes during the early phase of AD, as shown with other biomarkers associated with processes upstream of the AD pathomechanism, and decreases in expression as the disease progresses (34–36). Another possible explanation could be that the concentrations of neuronal injury/death biomarkers decrease after symptom onset, which suggests slowing of the acute neurodegenerative processes with symptomatic disease progression (37).
One limitation of the present study was the age difference between the AD and NC groups. However, we found that there was no correlation between MDS-OAβ levels and age in the 52 NC subjects (range 51–77, mean 60.5 ± 7.4), and speculated that age difference was not a significant variable in influencing MDS-OAβ levels. Second, the MMSE score of AD increased in patients with CDR 2 (Table 1), but this is thought to be due to the patients being of a younger age than those with CDR 1.