Visualization of Amyloid Oligomers in the Brain of Patients with Alzheimer's Disease

In the pathogenesis of Alzheimer's disease (AD), highly neurotoxic amyloid-r3 (Ar3) oligomers appear early, they are thus considered to be deeply involved in the onset of Alzheimer's dis-ease. However, Ar3 oligomer visualization is challenging in human tissues due to their multiple forms (e.g., low-and high-molecular-weight oligomers, including protofibrils) as well as their tendency to rapidly change forms and aggregate. In this review, we present two visualization approaches for Ar3 oligomers in tissues: an immunohistochemical (using the mono-clonal antibody TxCo1 against toxic Ar3 oligomer conformers) and imaging mass spectrometry using the small chemical Shiga-Y51 that specifically binds Ar3 oligomers. TxCo1 immunohistochemistry revealed Ar3 oligomer distributions in postmortem human brains with AD. Using Shiga-Y51, imaging mass spectrometry revealed Ar3 oligomer distributions in the brain of a transgenic mouse model for AD. These two methods would potentially contribute to elucidating the pathological mechanisms underlying AD.