Lecanemab alters basement membrane collagen IV in viable microvessels isolated from brains with high Alzheimer's disease neuropathology

Amyloid-β (Aβ) can deposit in or near the microvascular basement membrane (BM) in Alzheimer's disease (AD). We examined the effect of the Aβ binding antibody, lecanemab, on BM collagen IV (Col-IV) using viable brain microvessels (MV) isolated from human postmortem brain tissue with high AD neuropathologic change (ADNC=3, 16 females (mean 86 years), 11 males (mean 81 years)). MVs were exposed to lecanemab or isotype for 4 days and examined for Col-IV related outcomes: western blotting, capillary electrophoresis, RT-PCR, and degraded Col-IV. We find a subset of MV from some donors demonstrate Col-IV changes that could cause microvascular injury when exposed to lecanemab.