| Sumario: | Participants: S.-M. Wang, D. W. Kang, Y. H. Um, N.-Y. Kim, H. K. Lim (All from Republic of Korea) Purpose: Exploration of Alzheimer's disease (AD) pathology by investigating beta-amyloid, tau, and neurodegeneration are effective in detecting AD at its preclinical phase. However, PET imaging of amyloid, tau, and FDG requires high cost whereas cerebrospinal fluid studies of Aβ42, phosphorylated tau, and total tau are invasive. Beta-amyloid (Aβ) is formed when beta-amyloid precursor protein (APP) is cleaved by beta- and gamma-secretase. Among diverse Aβs, Oligomerized Aβ (OAβ) is known to be the most toxic and is strongly associated with the earlier pathogenesis of AD. Multiple validation studies showed that the Multimer Detection System-Oligomeric Aβ (MDS-OAβ) technique can measure the oligomerization dynamics of Aβ in a plasma sample. We aimed to investigate whether MDS-OAβ can reflect cerebral Aβ deposition in cognitively normal older adults. Method: A total of 64 cognitively normal older adults who visited Catholic Brain Healthcare Center, Yeouido St. Mary's Hospital, for medical check-up complaining of cognitive decline were included in the study. Cerebral amyloid statuses were dichotomized into positive or negative based on visual assessment of amyloid positron emission topography (PET) scan (A-PET positive group=40, A-PET negative group=24) using [18F] flutemetamol. All participants received the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K). Plasma OAβ concentration was measured by MDS-OAβ. Results: Baseline demographic data of A-PET positive group and A-PET negative group showed no significant difference in gender, age, education, and cognitive function measured using CERAD-K. The plasma MDS-OAβ value was statistically higher in A-PET positive group (0.992 + 0.186) than in A-PET negative group (0.808 + 0.265) (p<0.01). Global cerebral Aβ retention correlated positively with plasma MDS-OAβ level. Plasma OAβ concentration higher than or equal to 0.90 ng/mL, the cut-off value which was established in a previous validation study, was defined as MDS-OAβ positive. MDS-OAβ positive group (N=38) showed higher cerebral global cerebral Aβ retention than MDS-OAβ negative group (N=26), but the difference was not statistically significant (p = 0.09). However, when patients having equivocal plasma MDS-OAβ value (0.85 ~ 0.89 ng/mL, N=4) were excluded, the difference of global cerebral Aβ retention between two groups became statistically significant (p<0.05). CONCLUSION: The plasma MDS-OAβ value might reflect cerebral amyloid status and global cerebral Aβ retention in cognitively normal older adults. This suggests that the plasma MDS-OAβ test might be considered an adjuvant or alternative to A-PET scan for cognitively normal older adults in clinical settings. However, longitudinal follow-up studies, investigating association between change of plasma MDS-OAβ with that of cerebral Aβ retention value, are needed to better understand clinical utility of plasma MDS-OAβ.
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