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

Abstract

Alzheimer's disease (AD), as the most common progressive neurodegenerative disorder, is pathologically characterized by deposition of extracellular plaque composed of amyloid-β peptide (Aβ). Different assembled states of Aβ have been considered as both important biomarkers and drug targets for the diagnosis and therapy of AD. Recent studies demonstrate that small, diffusible Aβ oligomers formed by aggregation of Aβ monomers are the major toxic agents in AD. Therefore, the development of reliable assays for Aβ (both monomers and oligomers) will be important for the early differential diagnosis of dementia, predicting the progression of AD, as well as monitoring the effectiveness of novel anti-Aβ drugs for AD. In this review, we summarize the recent progress made in the development of techniques for detection of Aβ monomers and oligomers. In particular, the principles governing the design of these sensors are classified and summarized. Moreover, the advantages and disadvantages of the assays are evaluated. This review also discusses the improvements and challenges for application of these assays in the early diagnosis of AD.

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

“…22,23 Therefore, the direct detection of Aβ oligomer level would be more reliable for AD diagnosis than assay of its monomer. 24,25 Recently, a few novel biosensors have been developed for the detection of Aβ oligomer, including electrochemistry, [26][27][28][29] surface plasma resonance (SPR), 30 localized surface plasmon resonance (LSPR), 24,31 fluorescence, 32,33 nuclear magnetic resonance, 34 and surface-enhanced Raman spectroscopy. 35 These methods are feasible, but they require the use of special instruments and/or relatively expensive and variable antibodies for the capture and recognition of Aβ oligomer.…”

Mass spectrometry is a multifaceted weapon to be used in the battle against Alzheimer's disease: Amyloid beta peptides and beyond

“…Accumulation and aggregation of Aβ peptides have been firstly proposed as the major culprit for the development of AD and, although many other factors (see below, section 2) are now largely recognized to be also crucial for the disease, characterization as well as quantification of Aβ peptide levels in their various oligomeric forms for diagnostic purposes have been primarily and widely investigated for many years in a variety of biological fluids and with many different analytical approaches . Here, we discuss only the MS analytical methods applied to find reliable AD biomarkers based on the quantification of Aβ peptides, whereas in subsection 1.3, more recent applications of MS for the characterization of the various Aβ species are discussed.…”

Potential therapeutics of Alzheimer's diseases: New insights into the neuroprotective role of trehalose‐conjugated beta sheet breaker peptides

“…A variety of small peptides that inhibit aggregation of Aβ and reduce its toxic effects have been already described and some of them showed to be effective in AD rodent animal models . Moreover, Aβ binding peptides have been proposed for suitable uses in in vivo imaging and early diagnosis of AD …”