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Amyloid‐beta Induced Endothelial‐Monocyte Interactions Involved in Alzheimer’s Disease
Author(s) -
Gonzalez Francisco Jose,
ReyesBarcelo Adriana,
Moss Melissa A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1153-c
Subject(s) - amyloid beta , amyloid (mycology) , cerebral amyloid angiopathy , thioflavin , chemistry , monocyte , presenilin , biochemistry of alzheimer's disease , alzheimer's disease , fibril , senile plaques , amyloid precursor protein , beta (programming language) , biophysics , microbiology and biotechnology , biochemistry , pathology , peptide , medicine , immunology , biology , disease , dementia , computer science , programming language , inorganic chemistry
Cerebral amyloid angiopathy (CAA) associated with Alzheimer’s disease (AD) is characterized by cerebrovascular deposition of the fibrillar form of the amyloid‐beta protein, assembled from amyloid‐beta monomer. Vascular amyloid‐beta accumulation initiates a cascade of events culminating in weakening of the vessel wall and increased risk of hemorrhagic stroke. Among these events is an increase in vessel‐associated monocyte/macrophage cells, which could promote vascular damage and may contribute to elevated immune responses observed in AD brain. We have investigated the ability of interactions between amyloid‐beta and endothelial monolayers to enhance adhesion and subsequent transmigration of monocyte cells. Treatment of endothelial monolayers with amyloid‐beta aggregation mixtures, containing mature fibrils, protofibril intermediates, and unassembled monomer, enhances monocyte adhesion and promotes subsequent transmigration. In contrast, treatment with either amyloid‐beta fibril or monomer alone has no effect. These results demonstrate that the presence of aggregated amyloid‐beta is insufficient to stimulate endothelium. Monomeric amyloid‐beta and protofibrils were purified on a SEC Superdex 75 column. Aggregation was monitored by thioflavin T fluorescence and dynamic light scattering. Support by a grant from the American Heart Association.