Isomerized Aβ in the brains can distinguish the status of amyloidosis in the Alzheimer’s Disease continuum

Isomerized N-terminus Aβ (Aβ_1-15) is a common feature of parenchymal amyloid deposits in the brain. Our results suggest Aβ deposits associated with early AD neuropathologic changes are distinct to the mature plaques found in AD, a consequence of prolonged deposition in the later. Our results have implications for early therapeutic targeting of these modified species as well potential for better biofluids biomarker development to track drug efficacy. References 1. Mukherjee S, Perez KA, Lago LC, et al. Quantification of N-terminal amyloid-β isoforms reveals isomers are the most abundant form of the amyloid-β peptide in sporadic Alzheimer's disease. Brain Commun. 2021;3(2). https://doi.org/10.1093/braincomms/fcab028 2. Mukherjee S, Perez KA, Dubois C, et al. Citrullination of Amyloid-β Peptides in Alzheimer's Disease. ACS Chem Neurosci. 2021;12(19):3719-3732. https://doi.org/10.1021/acschemneuro.1c00474 3. Mukherjee S, Fjeldsted JC, Masters CL, Roberts BR. Enhanced ion mobility resolution of Abeta isomers from human brain using high-resolution demultiplexing software. Anal Bioanal Chem. Published online April 15, 2022. https://doi.org/10.1007/s00216-022-04055-x.