Neuroinflammation in plaque and vascular β-amylold disorders:: Clinical and therapeutic implications

Backgroun: The cerebral P-amyloid (A beta) disorders show a great variability in the distribution of parenchymal and vascular amyloid deposits. Objective: To study the relationship between amyloid deposition and inflammatory responses in three distinct subtypes of cerebral A beta disorders. Methods: The distribution of inflammatory proteins and cells in vascular and plaque amyloid deposits was evaluated in postmortem brain tissue using immunohistochemistry. The effects of a mixture of A beta peptides and inflammation-related A beta-associated proteins were studied in postmortem obtained human microglia cell cultures. Results: The chronic inflammatory response is associated with amyloid plaques (but not with amyloid in the walls of larger vessels) in Alzheimer's disease (AD), with amyloid in cerebral arteries in hereditary cerebral hemorrhage with amyloidosis-Dutch type and with amyloid microangiopathy in the vascular variant of AD. A beta(1-42) fibrils complexed with complement factor C1q and serum amyloid P component (the relevant amyloid-associated proteins) stimulate the production of proinflammatory cytokines in human microglia cell cultures and this production is attenuated by minocycline. Conclusion: The pattern of the chronic inflammatory response associated with fibrillar A beta is strikingly different in the three studied types of A beta disorders. The site of the fibrillar A beta-induced chronic inflammatory response is closely related to clinical symptoms. Minocycline is a drug of interest to inhibit microglia-mediated neuroinflammatory response in A beta brain disorders. Copyright (c) 2008 S. Karger AG, Basel.