The LPS receptor (CD14) links innate immunity with Alzheimer's disease.
To rapidly respond to invading microorganisms, humans call on their innate immune system. This occurs by microbe-detecting receptors, such as CD14, that activate immune cells to eliminate the pathogens. Here, we link the lipopolysaccharide receptor CD14 with Alzheimer's disease, a severe neurodegenerative disease resulting in dementia. We demonstrate that this key innate immunity receptor interacts with fibrils of Alzheimer amyloid peptide. Neutralization with antibodies against CD14 and genetic deficiency for this receptor significantly reduced amyloid peptide induced microglial activation and microglial toxicity. The observation of strongly enhanced microglial expression of the LPS receptor in brains of animal models of Alzheimer's disease indicates a clinical relevance of these findings. These data suggest that CD14 may significantly contribute to the overall neuroinflammatory response to amyloid peptide, highlighting the possibility that the enormous progress currently being made in the field of innate immunity could be extended to research on Alzheimer's disease.
Department of Neurology, University of Goettingen, 37075 Goettingen, FRG. klaus.fassbender@med.uni-goettingen.de
K
K
Fassbender
S
S
Walter
S
S
Kühl
R
R
Landmann
K
K
Ishii
T
T
Bertsch
A K
AK
Stalder
F
F
Muehlhauser
Y
Y
Liu
A J
AJ
Ulmer
S
S
Rivest
A
A
Lentschat
E
E
Gulbins
M
M
Jucker
M
M
Staufenbiel
K
K
Brechtel
J
J
Walter
G
G
Multhaup
B
B
Penke
Y
Y
Adachi
T
T
Hartmann
K
K
Beyreuther
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D007113:Immunity, Innate; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D018950:Lipopolysaccharide Receptors; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)