Abstract Background Multimer detection system‐oligomeric amyloid‐ß (MDS‐OAß) measures plasma OAß level and is associated pathology of Alzheimer’s disease (AD). However, no study investigated MDS‐OAß and cerebral Aß deposition among difference stages within AD spectrum. Method We studied 40 normal control (CN), 30 amyloid‐PET (A‐PET) negative mild cognitive impairment (MCI), 31 A‐PET positive MCI, and 22 A‐PET positive dementia. Result The one‐way analysis of variance showed group difference in MDS‐OAß. Post‐hoc analysis showed that MDS‐OAß was lowest in CN group and highest in A‐PET positive MCI group. Both A‐PET negative MCI and A‐PET positive dementia groups showed lower MDS‐OAß than A‐PET positive group dementia group (MDS‐OAß: CN < A‐PET negative MCI = A‐PET positive dementia < A‐PET positive MCI) (Figure 1). MDS‐OAß showed a positive correlation with global and regional cerebral Aß deposition measure using A‐PET. Conclusion Our results suggest that MDS‐OAβ shows a reverse U‐shape: increase with disease onset or when clinical symptoms appear, even before Aß pathology is evident in A‐PET, and then elevate as disease progresses but lower down as the disease becomes severe.