Circulating Claudin-5 Correlates with Age and Alzheimer ' s Disease

In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). The BBB functions as a selective gate for the uptake of essential molecules from blood into the brain and the excretion of harmful molecules from the brain into blood via transporters and receptors on cellular membranes. In addition, the BBB prevents the influx of blood-borne neurotoxins, cells, and pathogens into the brain because of the formation of tight junctions (TJs) in the intercellular space between adjacent macrovascular endothelial cells. Loss of BBB integrity has been observed in neuroinflammatory disorders, and patients with early AD demonstrate BBB leakage. In addition, patients with early cognitive dysfunction show BBB breakdown in the hippocampus, which occurs independently of brain accumulation of amyloid and tau. These several findings indicate that BBB TJ-sealing components might be impaired in MCI- and AD-related pathology. Breakdown of the BBB, which is associated with CNS diseases, is accompanied by the invasion of leukocytes and activation of astrocytes. The matrix metalloproteinases (MMPs) secreted by these invading leukocytes have been shown to lead to the degradation of CLDN-5 in the BBB of mice. In a rat ischemic model, MMPs secreted from ...
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