Uptake of Abeta 1-40- and Abeta 1-42-coated yeast by microglial cells: a role for LRP.
Artificial diffuse and amyloid core of neuritic plaques [beta-amyloid peptide (Abeta) deposits] could be prepared using heat-killed yeast particles opsonized with Abeta 1-40 or Abeta 1-42 peptides. Interaction and fate of these artificial deposits with microglial cells could be followed using a method of staining that allows discrimination of adherent and internalized, heat-killed yeast particles. Using this system, it was possible to show that nonfibrillar or fibrillar (f)Abeta peptides, formed in solution upon heating (aggregates), could not impair the internalization of heat-killed yeast particles opsonized with fAbeta 1-40 or fAbeta 1-42. This indicated that depending on their physical state, Abeta peptide(s) do not recognize the same receptors and probably do not follow the same internalization pathway. Using competitive ligands of class A scavenger receptors (SR-A) or low-density lipoprotein-related receptor protein (LRP), it has been shown that SR-A were not involved in the recognition of amyloid peptide deposits, whereas LRP specifically recognized deposits of fAbeta 1-42 (but not fAbeta 1-40) and mediated their phagocytosis.
Laporte
Vincent
V
Laboratoire de Pathologie des Communications entre Cellules Nerveuses et Musculaires, EA 3429, Faculté de Pharmacie, Université Louis Pasteur, 74, route du Rhin-BP 24, F-67401 Illkirch, Cedex, France.
Lombard
Yves
Y
Levy-Benezra
Rachel
R
Tranchant
Christine
C
Poindron
Philippe
P
Warter
Jean-Marie
JM
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear