Development of Alzheimer's disease biomarker using Aβ* 56 soluble oligomer in human nasal secretions

Abstract

Background: Although soluble Aβ oligomer (AβO) might play a pivotal role in pathogenesis of Alzheimer's disease (AD), development of biomarker using detection of AβO might be limited due to its structural heterogeneity. Recently, we found the 56kDa soluble Aβ*56(Aβ*56) which is known to be involved in a very early sate of AD in human nasal secretion. The aim of this study is to explore diagnostic validity of Aβ*56 in nasal secretions in discriminating AD pathology.

Method: A total of 28 patients (normal control (NC) = 9, amnestic mild cognitive impairment (aMCI) = 10, and AD = 9) were included in the study. They were dichotomized using 18F-Flutemetamol amyloid positron emission tomography (PET) into with and without detectable amyloid burden. Level of Aβ*56 in nasal secretions were measured using immune blotting. Group differences in nasal Aβ*56 level were analyzed and correlation between nasal Aβ*56 level and mean standardized uptake value ratio were also conducted.

Result: There were no group differences in age, gender, and education. The nasal Aβ*56 level were significantly higher in aMCI and AD than NC group, but no group differences were found between aMCI and dementia. The nasal Aβ*56 level also had a positive correlation with cortical Aβ deposition on 18F-Flutemetamol PET.

Conclusion: These results demonstrate that the nasal Aβ*56 level can be easily measured, and it may be utilized as a biomarker for the diagnosis of early AD including aMCI. The study also suggests that nasal Aβ*56 level may predict cortical deposition of Aβ.