Amyloid beta oligomers from human Alzheimer’s disease brain isolated by immunoaffinity chromatography

Immunoaffinity chromatography confirms that, as with synthetic AβOs, the AβOs in AD brain targeted by ACU193 are globular. r-mAb148, the murine precursor of Leqembi, isolates globular and protofibrillar AβOs, extending reports that affinity purification yields fibrils from AD brain. ACU193 also recognizes protofibrils found in 5xFAD but not human brain. Experiments are in progress to evaluate the impact of chromatography method and extract preparation on particle morphology, to evaluate pathological impact in cell assays, to determine oligomer substructures by native mass spectrometry, and to determine high-resolution structural details by cryoEM.