Plasma amyloid-beta oligomer is related to subjective cognitive decline and brain amyloid status

Background Subjective cognitive decline (SCD) is a target for Alzheimer's disease prediction. Plasma amyloid-beta oligomer (A beta O), the pathogenic form of A beta in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain A beta deposition. The relationship between plasma A beta O, brain A beta deposition, and SCD in individuals with normal objective cognition has not been investigated. Methods In this cross-sectional study, we analyzed 126 participants with normal objective cognition. More SCD symptoms were expressed as higher scores of the Subjective Cognitive Decline Questionnaire (SCDQ) and Memory Age-associated Complaint Questionnaire (MACQ). The plasma A beta O level of each participant was measured twice for validation and expressed as a concentration (ng/mL) and a ratio relative to the mean value of two internal standards. Brain A beta deposition was assessed by [F-18] flutemetamol positron emission tomography (PET) and expressed as standard uptake value ratio (SUVR). Associations of SCDQ and MACQ with plasma A beta O levels or SUVR were analyzed in multiple linear regression models. The association between plasma A beta O level and flutemetamol PET positivity was assessed in logistic regression and receiver operative characteristic analyses. Results Overall, participants were 73.3 years old with female predominance (69.0%). After adjustment for confounders, high SCDQ and MACQ scores were associated with the high plasma A beta O levels as both concentrations and ratios (ratios: standardized coefficient = 0.246 and p = 0.023 for SCDQ, standardized coefficient = 0.209 and p = 0.029 for MACQ; concentrations: standardized coefficient = 0.257 and p = 0.015 for SCDQ, standardized coefficient = 0.217 and p = 0.021 for MACQ). In contrast, SCDQ and MACQ were not significantly associated with SUVRs (p = 0.134 for SCDQ, p = 0.079 for MACQ). High plasma A beta O levels were associated with flutemetamol PET (+) with an area under the curve of 0.694 (ratio) or 0.662 (concentration). Combined with APOE e4, plasma A beta O presented area under the curves of 0.789 (ratio) and 0.783 (concentration). Conclusions Our findings indicate that the high plasma A beta O level could serve as a potential surrogate biomarker of severe SCD and the presence of brain A beta deposition in individuals with normal objective cognition.

Automated summary

This study found that high plasma AβO levels could potentially serve as a surrogate biomarker for severe SCD and the presence of brain Aβ deposition in individuals with normal objective cognition.