posted on 2021-02-12, 01:03authored byYuemei Duan, Jia Chen, Yan Jin, Qiuyun Tu, Shuhui Wang, Juan Xiang
Alzheimer’s disease (AD) is
the most common neurodegenerative
disease among the elderly. Abnormal aggregates of both β-amyloid
peptide (Aβ) subtypes, Aβ42 and Aβ40, are the typical neuropathology hallmarks of AD. However,
because of the lack of specific recognition elements such as an antibody
and aptamer, it is difficult to differentiate and determine the oligomers
of Aβ42 and Aβ40 in clinic. In this
paper, we developed a planar bilayer lipid membrane (BLM)-based electrochemical
biosensor. According to the dynamic differences on oligomer-induced
BLM damage, both low-mass, soluble oligomers of Aβ42 and Aβ40 (L-Aβ42O and L-Aβ40O) were measured in turn by electrochemical impedance spectroscopy.
The BLM was supported by a porous 11-mercaptoundecanoic acid layer
on a gold electrode, which amplified the impedance signal corresponding
to the membrane damage and improved the detection sensitivity. The
weakly charged surface of the BLM ensured the low non-specific adsorption
of coexisting proteins in cerebrospinal fluid (CSF). Using the electrochemical
biosensor, L-Aβ42O was determined within 20 min,
with a linear range from 5 to 500 pM and a detection limit of 3 pM.
Meanwhile, L-Aβ40O was determined within 60 min,
with a linear range from 60 pM to 6.0 nM and a detection limit of
26 pM. The recoveries in oligomer-spiked artificial CSF and human
CSF samples confirmed the accuracy and applicability of this proposed
method in clinic. This work provides an antibody-free, highly selective,
and sensitive method for simultaneous detections of L-Aβ42O and L-Aβ40O in real CSF samples, which
is significant for the early diagnosis and prognosis of AD.