Neuroinflammation in Plaque and Vascular β-Amyloid Disorders: Clinical and Therapeutic ImplicationsEikelenboom P.a, b · Veerhuis R.b, c · Familian A.b · Hoozemans J.J.M.d · van Gool W.A.a · Rozemuller A.J.M.d, e
aDepartment of Neurology, Academic Medical Center, University of Amsterdam, Departments of bPsychiatry, cClinical Chemistry and dPathology, VU University Medical Center, Vrije Universiteit, Amsterdam, and eDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
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Background: The cerebral β-amyloid (Aβ) 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 Aβ 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 Aβ peptides and inflammation-related Aβ-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. Aβ1–42 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 Aβ is strikingly different in the three studied types of Aβ disorders. The site of the fibrillar Aβ-induced chronic inflammatory response is closely related to clinical symptoms. Minocycline is a drug of interest to inhibit microglia-mediated neuroinflammatory response in Aβ brain disorders.
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