Elevated plasma levels of exosomal BACE1-AS combined with the volume and thickness of the right entorhinal cortex may serve as a biomarker for the detection of Alzheimer's disease

Long non-coding RNA (lncRNA) and exosomes are involved in the pathological process of Alzheimer's disease (AD), the pathological changes of which are usually first observed in the entorhinal cortex and hippocampus. The aim of the present study was to determine whether the measurement of plasma exosomal lncRNA combined with image data of the entorhinal cortex and hippocampus could be used as a biomarker of AD. A total of 72 patients with AD and 62 controls were recruited, and the expression levels of several lncRNAs were assessed. Of the recruited participants, 22 patients and 26 controls received brain 3D-BRAVO sequence magnetic resonance imaging (MRI) scans, which were analyzed using an automated analysis tool. The plasma exosomal β-site amyloid precursor protein cleaving enzyme-1-antisense transcript (BACE1-AS) levels in patients with AD were significantly higher compared with the controls (P<0.005). Receiver operating characteristic curve analysis revealed that the area under the curve (AUC) was 0.761 for BACE1-AS, the sensitivity was 87.5%, and the specificity was 61.3%. Analysis of MRI images indicated that the right entorhinal cortex volume (P=0.015) and thickness (P=0.022) in patients with AD were significantly smaller. The AUC was 0.688 for the right entorhinal cortex volume, with a sensitivity of 59.1%, and the specificity was 84.6%. The AUC was 0.689 for right entorhinal cortex thickness, with a sensitivity of 80.8%, and the specificity was 59.1%. A series-parallel test which integrated the BACE1-AS with the right entorhinal cortex volume and thickness, raised the specificity and sensitivity to 96.15 and 90.91%, respectively. A logistic regression model demonstrated that combination of the 3 indices provided improved sensitivity and specificity simultaneously, particularly when adjusting for age and sex (AUC, 0.819; sensitivity, 81%; specificity, 73.1%). The results of the present study demonstrated that detection of plasma exosomal BACE1-AS levels combined with the volume and thickness of the right entorhinal cortex may be used as a novel biomarker of AD.