Amyloid beta protein (A beta) removal by neuroglial cells in culture.
Because the mechanisms of A beta degradation in normal and Alzheimer's disease brain are poorly understood, we have examined whether various cortical cells are capable of processing this peptide. Rat microglia and astrocytes, as well as the human THP-1 monocyte cell line, degraded A beta 1-42 added to culture medium. In contrast, neither rat cortical neurons or meningeal fibroblasts effectively catabolized this peptide. When A beta fibrils were immobilized as plaque-like deposits on culture dishes, both microglia and THP-1 cells removed the peptide. Astrocytes were incapable of processing the A beta deposits, but these cells released glycosaminoglycase-sensitive molecules that inhibited the subsequent removal of A beta by microglia. This implied that astrocyte-derived proteoglycans associated with the amyloid peptide and slowed its degradation. The addition of purified proteoglycan to A beta that was in medium or focally deposited also resulted in significant inhibition of peptide removal by microglia. These data suggest that A beta can be catabolized by microglia and proteoglycans which co-localize with senile plaques may slow the degradation of A beta within these pathologic bodies.
Shaffer
L M
LM
Gliatech, Inc., Cleveland, OH 44122, USA.
Dority
M D
MD
Gupta-Bansal
R
R
Frederickson
R C
RC
Younkin
S G
SG
Brunden
K R
KR
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D011509:Proteoglycans