Aggregation of β-amyloid (Aβ) were considered as a typical pathological feature of Alzheimer's disease (AD). Extensive studies have verified that soluble Aβ oligomers (AβO) were more toxic to neurons than plaques. Herein, in this work, a glucose entrapped liposome-based portable aptasensor was fabricated for recognizing and interacting with AβO by specific aptamer on liposome (G-Lip-Apt). Then, a single strand DNA, designed to be partially complementary to AβO aptamer, was modified on amino-functionalized Fe3O4@SiO2 to obtain a magnetic nanocomposite (Fe3O4@SiO2/NH2-DNA). In the presence of AβO, the specific recognition between AβO and its aptamer on G-Lip-Apt made AβO bounded with G-Lip-Apt. With subsequent introduction of Fe3O4@SiO2/NH2-DNA, the unreacted G-Lip-Apt was further linked with Fe3O4@SiO2/NH2-DNA by double stranded complementary pairing interaction. Along with the addition of TritonX-100 into the formed G-Lip-Apt/Fe3O4@SiO2/NH2-DNA complex, the encapsulated glucose was released from liposome and then measured by a personal glucose meter (PGM). Good linear correlation was acquired over concentration of 5.0-1000 nM and the limit of detection (LOD) was calculated to be 2.27 nM for AβO. The developed portable electrochemical strategy integrated magnetic separation, competitive reaction and point of care test (POCT) to achieve high sensitivity, selectivity and accuracy, therefore enabled it successfully applied to the analysis of AβO in the hippocampus and cortex of APP/PS1 transgenic AD mice.