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Soluble aggregates of the amyloid‐β protein selectively stimulate permeability in human brain microvascular endothelial monolayers
Author(s) -
GonzalezVelasquez Francisco J.,
Kotarek Joseph A.,
Moss Melissa A.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05618.x
Subject(s) - permeability (electromagnetism) , chemistry , amyloid (mycology) , human brain , vascular permeability , biophysics , neuroscience , biochemistry , biology , endocrinology , membrane , inorganic chemistry
Cerebral amyloid angiopathy associated with Alzheimer’s disease is characterized by cerebrovascular deposition of the amyloid‐β protein (Aβ). Aβ elicits a number of morphological and biochemical alterations in the cerebral microvasculature, which culminate in hemorrhagic stroke. Among these changes, compromise of the blood‐brain barrier has been described in Alzheimer’s disease brain, transgenic animal models of Alzheimer’s disease, and cell culture experiments. In the current study, presented data illustrates that isolated soluble Aβ 1–40 aggregates, but not unaggregated monomer or mature fibril, enhance permeability in human brain microvascular endothelial monolayers. Aβ 1–40 ‐induced changes in permeability are paralleled by both a decrease in transendothelial electrical resistance and a re‐localization of the tight junction‐associated protein zonula occludin‐1 away from cell borders and into the cytoplasm. Small soluble Aβ 1–40 aggregates are confirmed to be the most potent stimulators of endothelial monolayer permeability by establishing an inverse relationship between average aggregate size and stimulated changes in diffusional permeability coefficients. These results support previous findings demonstrating that small soluble Aβ 1–40 aggregates are also primarily responsible for endothelial activation, suggesting that these same species may elicit other changes in the cerebrovasculature associated with cerebral amyloid angiopathy and Alzheimer’s disease.