Elevated soluble amyloid beta protofibrils in Down syndrome and Alzheimer's disease

Abstract

Down syndrome (DS) is caused by trisomy of chromosome 21, which leads to a propensity to develop amyloid β (Aβ) brain pathology in early adulthood followed later by cognitive and behavioral deterioration. Characterization of the Aβ pathology is important to better understand the clinical deterioration of DS individuals and to identify interventive strategies. Brain samples from people with DS and Alzheimer's disease (AD), as well as non-demented controls (NDC), were analyzed with respect to different Aβ species. Immunohistochemical staining using antibodies towards Aβ was also performed. Elevated levels of soluble Aβ protofibrils and insoluble Aβx-40 and Aβx-42 in formic acid brain extracts, and elevated immunohistochemical staining of Aβ deposits were demonstrated with the antibody BAN2401 (lecanemab) in DS and AD compared with NDC. These data and the promising data in a large phase 2 CE clinical trial with lecanemab suggest that lecanemab may have the potential to preserve cognitive capacity in DS. Lecanemab is currently in a phase 3 CE clinical trial.