Recovered astrocyte-vascular communication in the hippocampus of AD-mice after glycan-binding protein Galectin-1 treatment

PRESA J; POMILIO C; VINUESA A; GREGOSA A; BENTIVEGNA M; GONZALEZ PEREZ N; BELLOTTO M; SOIZA REILLY M; BEAUQUIS J; RABINOVICH G; SARAVIA F

Porto

Congreso; ISN-ESN 2023 Meeting; 2023

International Society for Neurochemistry

Cerebral amyloid angiopathy (CAA) is caused by amyloid perivascular deposition. In Alzheimer´s Disease (AD), CAA is found in arteries, arterioles and capillaries, being detrimental to their function. AD´s vascular alterations correlate with disease progression. Clinical interventions would benefit from preventing or restoring vascular changes. Galectins, a family of galactoside-binding proteins, are involved in survival, immune and vascular pathways. Galectin-1 (Gal1) positive effects on an autoimmune encephalomyelitis model, lead us to explore a potential role in AD. Tg PDAPPJ20 mice, a model for CAA/AD, received a treatment of Gall (three weekly i.p. 9 injections of 100 ug/dose). Tg 12 m.o. mice vehicle-treated (Tg-Veh) showed considerable amyloid deposited around vessels on the hilus of the hippocampus, a highly vascularized region early susceptible in AD. However, Tg mice treated with Gall (Tg-Gal1) presented a 35% decrease compared to Tg-Veh (p < 0.05) without modifying vascular density and morphology. Clearance of B-amyloid from brain interstitium occurs mostly through the blood-brain barrier (BBB) and requires astrocytic-vessel interaction, as the endfeet wrapped around the vasculature contributes to vasomotion and fluid movement.While Tg-Veh mice showed a decrease in astrocyte feet-vessel contact vs NTg mice treated with vehicle, Tg-Gal1 mice presented a recuperation of the ensheathing of the vasculature, assessed by lectin staining and GAP IF analysis. In addition, we found recovery of the specific endfeet protein Aquaporin-4 in Tg-Gal1 (p