Chemical Fluorescent Probe for Detection of Aβ Oligomers

Abstract

Aggregation of amyloid β-peptide (Aβ) is implicated in the pathology of Alzheimer’s disease (AD), with the soluble, Aβ oligomeric species thought to be the critical pathological species. Identification and characterization of intermediate species formed during the aggregation process is crucial to the understanding of the mechanisms by which oligomeric species mediate neuronal toxicity and following disease progression. Probing these species proved to be extremely challenging, as evident by the lack of reliable sensors, due to their heterogeneous and transient nature. We describe here an oligomer-specific fluorescent chemical probe, BoDipy-Oligomer (BD-Oligo), developed through the use of the diversity-oriented fluorescent library approach (DOFLA) and high-content, imaging-based screening. This probe enables dynamic oligomer monitoring during fibrillogenesis in vitro and shows in vivo Aβ oligomers staining possibility in the AD mice model.

Detection of Aβ Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease

“…With the advancement of nanotechnology,f abrication methods should get us closer to finding aw ay for early diagnosis of AD. Ab oligomer electrochemistry peptiderecognition 0.048 nM high sensitivity nonspecific adsorption [74] Ab oligomer electrochemistry protein recognition 0.5 pM high sensitivity nonspecific adsorption [75] Ab oligomer electrochemistry antibodyr ecognitionnot detected simplicity nonspecific adsorption [76] Ab oligomer localized SPR antibodyr ecognition100 fM high sensitivity and simplicity nonspecific adsorption [80] Ab oligomer fluorescent sensor interaction with probenot detected simplicity low specificity [86,87] Ab oligomer large instruments SERS;MS not detected high sensitivity and selectivity expensive instrument, complex operation [95,96] …”

A sensitive and selective electrochemical biosensor for the determination of beta-amyloid oligomer by inhibiting the peptide-triggered in situ assembly of silver nanoparticles

“…36 Alternatively, the organic dye-based fluorescence assays (eg, thioflavin T [ThT]) have been commonly used for monitoring the formation of Aβ aggregates in laboratory investigation. 37,38 However, most of the dyes cannot be used to discriminate Aβ oligomer from other β-sheets of Aβ aggregates, 37 thus limiting their applications for the routine test of Aβ oligomer for early diagnosis of AD.…”

‘From past to future’ – deciphering the molecular basis of Alzheimer's disease through the pages of the Journal of Neurochemistry

“…An oligomer‐specific fluorescent chemical probe, BoDipy‐Oligomer, has been described which shows binding to ex vivo brain sections (Teoh et al . ). While a method based on electrochemical impedance spectroscopy suggests it is capable of specifically detecting Aβ oligomers (Rushworth et al .…”

“…Looking at the state of the field nearly 10 years on from that review shows that while there are still major gaps in our understanding of Ab oligomers, significant progress has been made. An oligomer-specific fluorescent chemical probe, BoDipy-Oligomer, has been described which shows binding to ex vivo brain sections (Teoh et al 2015). While a method based on electrochemical impedance spectroscopy suggests it is capable of specifically detecting Ab oligomers (Rushworth et al 2014), however, the effectiveness of this technique on human tissue samples has not yet been reported.…”