Galectin-1 improves cognition and reduces amyloid- deposits in an animal model of Alzheimer?s disease possibly by modulating microglia phenotype and increasing Ab clearance

CARLOS POMILIO; AGUSTINA ALAIMO; JUAN BEAUQUIS; ANGELES VINUESA; GREGOSA, AMAL; GABRIEL RABINOVICH; JESSICA PRESA; MELISA BENTIVEGNA; KWANG SIK KIM; FLAVIA E. SARAVIA

Congreso; The 10th IBRO World Congress of Neuroscience IBRO 2019; 2019

Alzheimer?s disease (AD) is the most common form of dementia associated with an imbalanced production and clearance ofamyloid- peptides (A). Amyloid deposition and neuroinflammation are recognized hallmarks in AD, affecting mainly brain cortexand hippocampus, in addition to microvascular alterations anddysfunction of the blood-brain barrier (BBB). The glycan-bindingprotein galectin-1 (Gal1) modulates immune and endothelial cellsin nervous system compartments, where a neuroprotective rolewas proposed in autoimmune encephalomyelitis. We study theimpact of Gal1 on the cognitive and histopathological state of ADmice. We administered Gal1 (9 i.p. injections of 100 ug/dose) orvehicle during 3 weeks to 12 months-old PDAPPJ20 transgenicmice, or non-transgenic controls. The Gal1 treated group significantly improved cognitive response in the Novel Object LocationRecognition test (p < 0.05). Amyloid+ area in the hippocampus wasdecreased by 53,5%. Microglia is actively involved in A phagocytosis. Gal1 treatment induced a reduction in the microglial activationscore employing morphological analysis in the dentate gyrus. Theintegrity of the BBB is essential to A clearance via the glymphaticsystem but could be altered by perivascular A deposits-mostlyA1?40. Using tomato lectin to label the hippocampal vasculature coupled with immunofluorescence against A peptides, wefound a 30% decrease of perivascular A (p < 0.05) in Gal1 treatedmice, without affecting vascular density, which could indicate augmented clearance. We are currently working to determine miceBBB integrity employing Evans Blue intravenous injections andexploring its permeability to cerebral parenchyma, and using anin vitro BBB model to determine whether A1?40 alters it at nontoxic concentrations. Human brain microvascular endothelial cellson a transwell membrane are used, monitored by Transendothelial Electrical Resistance (TEER) and permeability essays. We arealso investigating possible protective effects of Gal1 on barrier?sintegrity.