Neuroinflammation in plaque and vascular beta-amyloid disorders: clinical and therapeutic implications.
BACKGROUND
The cerebral beta-amyloid (Abeta) 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 Abeta 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 Abeta peptides and inflammation-related Abeta-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. Abeta(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.


CONCLUSIONS
The pattern of the chronic inflammatory response associated with fibrillar Abeta is strikingly different in the three studied types of Abeta disorders. The site of the fibrillar Abeta-induced chronic inflammatory response is closely related to clinical symptoms. Minocycline is a drug of interest to inhibit microglia-mediated neuroinflammatory response in Abeta brain disorders.
Eikelenboom
Piet
P
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. piete@ggzba.nl
Veerhuis
Rob
R
Familian
Atoosa
A
Hoozemans
Jeroen J M
JJ
van Gool
Willem A
WA
Rozemuller
Annemieke J M
AJ
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*
D016229:Amyloid beta-Peptides