RECOVERY OF ASTROCYTE-VASCULAR COMMUNICATION IN THE HIPPOCAMPUS OF MICE WITH CEREBRAL AMYLOID ANGIOPATHY FOLLOWING TREATMENT WITH THE GLYCAN-BINDING PROTEIN GALECTIN-1

PRESA, J; POMILIO, C; OSES, C; GREGOSA, A; BENTIVEGNA, M; BELLOTTO, M; GONZALEZ PEREZ, N; VINUESA, A; BEAUQUIS, J; LEVI, V; SOIZA REILLY, M; RABINOVICH, GA; SARAVIA, F

Mar del Plata

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2022

SAIC

Cerebral amyloid angiopathy (CAA) is caused by amyloid perivasculardeposition. In Alzheimer’s Disease (AD), CAA is found inarteries, arterioles and capillaries, being detrimental to their functionand correlating with disease progression. Clinical interventionswould benefit from restoring vascular changes. Galectins, a familyof b-galactoside-binding proteins, play key roles in regulating immune,neuronal and vascular circuits. The neuroprotective effectsof Galectin-1 (Gal1) in a model of CNS autoimmune inflammation,led us to explore its potential role in AD. Tg PDAPPJ20 mice-CAA/AD model- were treated with recombinant Gal1 (rGal1; three weeklyi.p. 9 injections; 100 ug). Vehicle-treated 12 months-old Tg-miceshowed large amyloid deposition around vessels on the hilus of thehippocampus, a highly vascularized region affected early duringAD. Notably, Tg mice treated with rGal1 (Tg-Gal1) exhibited a 35%decrease in amyloid deposition around vessels compared to Tg-Veh (p<0.05) without vascular alterations. Clearance of ss-amyloidfrom the brain interstitium occurred mostly through the blood-brainbarrier (BBB) and required astrocytic-vessel interaction, as the endfeet wrapped around the vasculature contributed to vasomotion andfluid movement. While Tg-Veh mice showed a decrease in astrocytefeet-vessel contact compared to NTg-Veh mice, Tg-Gal1 miceshowed marked recovery of the ensheathing of the vasculature, assessedby lectin staining and GFAP IF analysis. Also, recovery of thespecific endfeet protein Aquaporin-4 in Tg-Gal1 (p<0.02 vs Tg-Veh)was verified by quantitative analysis of AQP4-lectin associations usingarray tomography. To investigate the mechanistic basis of thiseffect, we assessed BBB integrity with Evans blue. Tg-Gal1 miceshowed lower vascular permeability to this dye compared to Tg-Vehmice (p<0.05). Our results support a central role for Gal1 in restoringBBB properties and endothelium-astrocytes communication in thehippocampus of AD mice.