Electrochemical detection of specific interactions between apolipoprotein E isoforms and DNA sequences related to...

Apolipoprotein E4 (ApoE4) has a key role on the onset and progression of Alzheimer's disease (AD), since it favours the deposition of toxic amyloid-beta (Aβ) aggregates in the brain. These effects might result from the interaction between ApoE4 and specific DNA promoters related to cellular autophagy pathways and to the expression of neuroprotective proteins, like sirtuin-1. Herein, we modified gold electrodes with mixed self-assembled monolayers of 6-mercapto-1-hexanol and thiolated DNA oligonucleotides related to CLEAR (associated with autophagic processes that enable the clearance of toxic species, such as Aβ) and SirT1 (related to the expression of sirtuin-1) promoter sequences. The interactions of the immobilized DNA sequences with isoforms of ApoE (ApoE4/ApoE3/ApoE2) were investigated by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) measurements. By monitoring current and charge transfer resistance (R_ct) variations, CLEAR showed to interact specifically with ApoE4, whereas SirT1 showed a higher affinity to ApoE4 compared to ApoE3 and ApoE2. To the best of our knowledge, this is the first report about the application of electrochemical techniques to investigate the sequence-specific interaction between ApoE isoforms and CLEAR and SirT1 oligonucleotides.