Alzheimer-like plaque formation by human macrophages is reduced by fibrillation inhibitors and lovastatin.
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.
Gellermann
Gerald P
GP
Leibniz Institute for Age Research, Fritz-Lipmann Institute, Beutenbergstrasse 11, D-07745 Jena, Germany.
Ullrich
Kathrin
K
Tannert
Astrid
A
Unger
Christiane
C
Habicht
Gernot
G
Sauter
Simon R N
SR
Hortschansky
Peter
P
Horn
Uwe
U
Möllmann
Ute
U
Decker
Michael
M
Lehmann
Jochen
J
Fändrich
Marcus
M
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
D000682:Amyloid; D008148:Lovastatin