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 (AbetaO), which are the primary neurotoxic species in AD. AbetaO have been proposed as the best biomarker for AD and levels of AbetaO 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 (PrP(C), residues 95-110), a highly expressed synaptic protein which mediates the neuronal binding and toxicity of AbetaO. During the layer-by-layer sensor construction, biotinylated PrP(C) (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 Abeta oligomers or monomers. The biosensor was specific for the detection of synthetic AbetaO and gave a linear response, without significant detection of monomeric Abeta, down to an equivalent AbetaO concentration of ~0.5 pM. The biosensor was also able to detect natural, cell-derived AbetaO present in conditioned medium. The eventual commercialisation of this biosensor system could allow for the early diagnosis and disease monitoring of AD. ; Rushworth, Jo V Ahmed, Asif Griffiths, Heledd H Pollock, Niall M Hooper, Nigel M Millner, Paul A England Biosens Bioelectron. 2014 Jun 15;56:83-90. doi: 10.1016/j.bios.2013.12.036. Epub 2013 Dec 24.