A label-free electrical impedimetric biosensor for the specific detection of Alzheimer's amyloid-beta oligomers

Alzheimer's disease (AD) is the most common form of dementia, with over 37 million sufferers worldwide and a global cost of over $600 billion. There is currently no cure for AD and no reliable method of diagnosis other than post-mortem brain examination. The development of a point-of-care test for AD is an urgent requirement in order to provide earlier diagnosis and, thus, useful therapeutic intervention. Here, we present a novel, label-free impedimetric biosensor for the specific detection of amyloid-beta oligomers (A beta O), which are the primary neurotoxic species in AD. A beta O have been proposed as the best biomarker for AD and levels of A beta O in the blood have been found to correlate with cerebrospinal fluid load. The biorecognition element of our biosensor is a fragment of the cellular prion protein (PrPc, residues 95-110), a highly expressed synaptic protein which mediates the neuronal binding and toxicity of A beta O. During the layer-by-layer sensor construction, biotinylated PrPc (95-110) was attached via a biotin/NeutrAvidin bridge to polymer-functionalised gold screen-printed electrodes. Electrochemical impedance spectroscopy (EIS), cyclic voltammetry and scanning electron microscopy were used to validate biosensor assembly and functionality. EIS was employed for biosensor interrogation in the presence of A beta oligomers or monomers. The biosensor was specific for the detection of synthetic A beta O and gave a linear response, without significant detection of monomeric A beta, down to an equivalent A beta O concentration of similar to 0.5 pM. The biosensor was also able to detect natural, cell-derived A beta O present in conditioned medium. The eventual commercialisation of this biosensor system could allow for the early diagnosis and disease monitoring of AD. (C) 2013 Elsevier B.V. All rights reserved.