Two amyloid-β peptides (Aβ40 and Aβ42) feature prominently in the extracellular brain deposits associated with Alzheimer's disease. While Aβ40 is the prevalent form in the cerebrospinal fluid, the fraction of Aβ42 increases in the amyloid deposits over the course of disease development. The low in vivo concentration (pM-nM) and metastable nature of Aβ oligomers have made identification of their...

Alzheimer’s disease (AD) is the most common form of dementia world-wide. The causative agent in this protein misfolding disease is the 39 to 42-residues long amyloid-b (Ab) peptide, that aggregates into oligomers, filaments, and fibrils found in plaque deposits in the brain of AD patients [1]. Up to now a viable cure for this disease is still not available. One reason for this is Ab’s conformat...

Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. The expression of phosphorylated neurofilament-H was significantly elevated in the hippocampal CA1. This indicates that oligomers induce an increase in the dens...

Chaperonins are large, essential, oligomers that facilitate protein folding in chloroplasts, mitochondria, and eubacteria. Plant chloroplast chaperonins are comprised of multiple homologous subunits that exhibit unique properties. We previously characterized homogeneous, reconstituted, chloroplast-chaperonin oligomers in vitro, each composed of one of three highly homologous beta subunits from ...

Soluble oligomers of the amyloid-β (Aβ) peptide cause neurotoxicity, synaptic dysfunction, and memory impairments that underlie Alzheimer disease (AD). The cellular prion protein (PrP(C)) was recently identified as a high affinity neuronal receptor for Aβ oligomers. We report that fibrillar Aβ oligomers recognized by the OC antibody, which have been shown to correlate with the onset and severit...

Six star-shaped oligomers containing triphenylamine (D1-D3) and benzene unit (D4-D6) as cores have been synthesized by Wittig condensation or Heck coupling reaction using aromatic aldehydes and triphenylphosphonium salts or aromatic halogenated compounds with vinyl triphenylamine. All oligomers have well-defined molecular structure and high purity. Characterization of the oligomers was made by ...

In Parkinson's disease (PD) and other α-synucleinopathies, prefibrillar α-synuclein (αS) oligomer is implicated in the pathogenesis. However, toxic αS oligomers observed using in vitro systems are not generally seen to be associated with α-synucleinopathy in vivo. Thus, the pathologic significance of αS oligomers to αS neurotoxicity is unknown. Herein, we show that, αS that accumulate within en...

Soluble oligomers are potent toxins in many neurodegenerative diseases, but little is known about the structure of soluble oligomers and their structure-toxicity relationship. Here we prepared onpathway oligomers of the 140-residue protein R-synuclein, a key player in Parkinson’s disease, at concentrations an order of magnitude higher than previously possible. The oligomers form ion channels wi...

We present here environmental factors including pH shifts, temperature, and metal ions surrounding Aβ40 monomer to precede the oligomers. We also suggest a new idea to detect Aβ40 oligomers with anti-Aβ40 monoclonal antibody using enzyme-linked immunosorbent assay. This method involves the different sensitivity of the thermal shifts between Aβ40 monomer and the oligomers. The idea is useful for...