title: Alzheimer-like plaque formation by human macrophages is reduced by fibrillation inhibitors and lovastatin.
abstract: The cerebral deposition of Abeta-peptide as amyloid fibrils and plaques represents a hallmark characteristic of Alzheimer's disease (AD). AD plaques are defined by their green birefringence after Congo red staining, their spherulite-like superstructure and their association with specific secondary components. Here we show that primary human macrophages promote the formation of amyloid plaques that correspond in all aforementioned characteristics to typical amyloid plaques from diseased tissues: they consist of aggregated Abeta-peptide, they reveal the typical ''Maltese cross" structure and they are associated with the secondary components glycosaminoglycanes, apolipoprotein E (apoE) and the raft lipids cholesterol and sphingomyelin. Plaque formation can be impaired in this cell system by addition of small molecules, such as Congo red, melantonine and lovastatin, suggesting potential applications for the study of cellular amyloid formation and for the identification or validation of drug candidates.
authors.affiliation: Leibniz Institute for Age Research, Fritz-Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Gellermann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Ullrich
authors.forename: Astrid
authors.initials: A
authors.lastname: Tannert
authors.forename: Christiane
authors.initials: C
authors.lastname: Unger
authors.forename: Gernot
authors.initials: G
authors.lastname: Habicht
authors.forename: Simon R N
authors.initials: SR
authors.lastname: Sauter
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.forename: Uwe
authors.initials: U
authors.lastname: Horn
authors.forename: Ute
authors.initials: U
authors.lastname: Möllmann
authors.forename: Michael
authors.initials: M
authors.lastname: Decker
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D018929:Cell Culture Techniques; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000682:Amyloid; D008148:Lovastatin