Loss of blood-brain barrier properties in association with endoplasmic reticulum stress in vascular cells from in vivo and in vitro models of Alzheimer's disease.

CARLOS POMILIO; JESSICA PRESA; ANGELES VINUESA; MELISA BENTIVEGNA; AMAL GREGOSA; JUAN BEAUQUIS; SARAVIA, FLAVIA

Congreso; Alzheimer's Association International Conference (AAIC); 2021

Alzheimer's Association

Background: Alzheimer’s disease (AD) is the leading cause of dementia. Among otherhistopathological hallmarks, it is characterized by the abnormal accumulation ofAmyloid-β (Aβ) peptides. Vascular alterations and blood-brain barrier (BBB) disruptionare also evidenced in AD patients, in close association with perivascular amyloiddeposits, which are composed mainly of Aβ 1-40. Aβ was linked to endoplasmic reticulumstress (ERS) induction in brain cells. In this study we characterized the progressionof vascular alterations in the hippocampus of PDAPP-J20 mice, a validated transgenicmodel for AD.Method: Brain sections from young and old PDAPP-J20 mice were processed forimmunohistochemistry against occludin or stained with fluorescent tomato lectin -avascular marker-. Some mice were previously injected with Evans blue or sodium fluoresceinin order to evidence BBB disruption. Also, cerebral microvascular fractionswere obtained from old PDAPP-J20 mice and the proteins from these samples wereanalyzed by mass spectrometry and proteomics analysis. For in vitro assays, humanbrain microvascular endothelial cells were exposed to fibrillar Aβ1-40. Markers forBBB and ERS were evaluated in these conditions.