Brain extracts were prepared and immunodepleted using the positive control 4G8 antibody, ALZ-201 or an isotype control to ALZ-201. The antibody’s potential for cross-protective activity against pathological Aβ was evaluated in brain tissue samples from 10 individuals confirmed as AD ( n =7) and non-AD ( n =3) with IHC staining for Aβ and phosphorylated tau (p-Tau) aggregates. Specificity for the oligomeric form of the Aβ42CC antigen and Aβ42 was confirmed using ELISA, and non-reactivity against plaques by immunohistochemistry (IHC). Mice were immunised with stable oligomers derived from the Aβ42 peptide with A21C/A30C mutations (AβCC), and ALZ-201 was developed using hybridoma technology. Subsequently, we assessed the etiological relevance of the Aβ targeted by ALZ-201 on physiologically derived, toxic Aβ using extracts from post-mortem brains of AD patients and controls in primary mouse neuron cultures. Here, we developed a monoclonal antibody with a unique oligomer-specific binding profile (ALZ-201) using oligomer-stabilising technology. Studies of such aggregates have been hampered by the lack of oligomer-specific research tools and their intrinsic instability and heterogeneity. In Alzheimer’s disease (AD), amyloid-β 1–42 (Aβ42) neurotoxicity stems mostly from its soluble oligomeric aggregates.
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