Image: Validation of beta-amyloid dimers in Alzheimer’s Brains (Photo courtesy of Institute for Research in Biomedicine).
The most widely used biomarkers for the early detection of Alzheimer's disease (AD) are currently the concentrations of beta-amyloid (Aβ) and phosphorylated Tau in cerebrospinal fluid. However, it has been observed that not all individuals with alterations in these biomarkers develop the disease.
Molecular exploration into AD had already established a correlation between the concentration of beta-amyloid dimers and the onset of the disease. Nevertheless the nature of these dimers has been hotly debated because it was not known whether the two beta-amyloid molecules that form the dimer were linked by a chemical bond or not.
Spanish and French scientists working with the Institute for Research in Biomedicine (Barcelona, Spain) validated a type of synthetic cross-linked Aβ (CL Aβ) dimers, obtained by means of the photoinduced cross-linking of unmodified proteins (PICUP) reaction, as well-defined mimics of putative brain CL Aβ dimers. They used these PICUP CL Aβ dimers as standards to improve the isolation of brain Aβ dimers and to develop state-of-the-art mass spectrometry (MS) strategies to allow their characterization. They then applied these MS methods to the analysis of brain Aβ dimer samples allowing the detection of the CL [Aβ(6–16)]2 peptide comprising a dityrosine cross-link. These findings were achieved using brain tissue samples from two patients with AD and a control.
The authors concluded that their result demonstrates the presence of CL Aβ dimers in the brains of patients with AD and opens up avenues for establishing new therapeutic targets and developing novel biomarkers for this disease. Aurelio Vázquez de la Torre, PhD, the lead author of study, said, “We have confirmed the potential of these dimers as biomarkers. We have found that the dimers are preserved during the tissue extraction procedure used in the lab and are consequently identical to those in the brains of patients with AD. Furthermore, we have developed a robust and sensitive method that allows us to study the dimers in any biological sample.” The study was published on April 3, 2018, in the journal Analytical Chemistry.
Institute for Research in Biomedicine