Investigating the Effects of an Amyloid-Binding Antibody on the Microvasculature in an Alzheimer's Disease Mouse Model

Alzheimer's disease (AD) is characterized by microvascular (MV) changes due, in part, to basement membrane (BM) alterations. Collagen IV (Col IV), a key BM structural protein, is often found near amyloid-beta (Aβ) deposition in AD, but their relationship remains unclear. Our project investigates how Aβ binding and removal using lecanemab (mAb158) affects MV structure and Col IV in 5xFAD mice, an AD model with extensive brain Aβ deposition. We hypothesized that Aβ removal disrupts Col IV, increasing MV damage and hemorrhage risk. To test this, we stained brain sections with hematoxylin and eosin (H&E) for acute hemorrhages and Prussian blue (PB) for subacute hemorrhages. Additionally, I performed immunohistochemistry (IHC) using collagen hybridizing peptide (CHP) for Col IV degradation and antibody 6E10 for Aβ deposition. In our preliminary results, we observed increased blood-brain-barrier (BBB) leakage at 20 mg/kg, but not at 10 mg/kg. H&E and PB indicated no acute or subacute hemorrhages in any of the groups. CHP levels were highest at 10 mg/kg, while 20mg/kg and isotype groups had levels similar to or slightly lower than the WT group. Contrastingly, Aβ decreased at 10 mg/kg but increased at 20 mg/kg, and was consistently higher in the lower cortex than in the upper cortex.