Macromolecules involved in production and metabolism of beta-amyloid at the brain barriers.
One of the notable features of Alzheimer's disease (AD) is the overabundance of beta-amyloid peptides in brain fluids, leading to the formation and deposition of insoluble amyloid plaques. Previous work in this lab demonstrates that the normal choroid plexus, a primary component of the blood-cerebrospinal fluid barrier, has the capacity to remove beta-amyloid from the cerebrospinal fluid, potentially preventing the formation of beta-amyloid plaques. The purpose of this work was to determine whether the choroid plexus and/or the brain capillaries, a primary component of the blood-brain barrier, possessed the capacity to produce or degrade beta-amyloid peptides. Using quantitative real-time RT-PCR, immunodetection and enzyme activity assays, we demonstrated the presence in brain barriers of several key enzymes involved in beta-amyloid production, namely, amyloid precursor protein and beta-secretase, and in beta-amyloid metabolism and alternate processing, such as insulin degrading enzyme, endothelin-converting enzyme-1, neprilysin and alpha-secretase. Furthermore, beta-amyloid presence, in the absence of its application in culture media, was detected in an immortalized choroidal epithelial cell line, known as Z310 cells. The ability of the choroid plexus to produce and degrade beta-amyloid, in addition to its transport function, suggests a vital role of this tissue in maintaining beta-amyloid homeostasis. Disruption of this homeostasis due to aging, injury or toxicant exposure may contribute to accumulation of beta-amyloid peptides in the brain fluids, leading to AD.
Crossgrove
Janelle S
JS
School of Health Sciences, Purdue University, 550 Stadium Mall Drive, CIVL-1163D, West Lafayette, IN 47907, USA.
Smith
Ellen L
EL
Zheng
Wei
W
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000201:enzymology / Q000378:metabolism; D002461:Cell Line, Transformed; D002829:Choroid / Q000166:cytology / Q000378:metabolism; D002831:Choroid Plexus / Q000201:enzymology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D007150:Immunohistochemistry; D046911:Macromolecular Substances / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D046911:Macromolecular Substances; D010446:Peptide Fragments; D053829:Amyloid Precursor Protein Secretases; D015260:Neprilysin