Declining expression of neprilysin in Alzheimer disease vasculature: possible involvement in cerebral amyloid angiopathy.
Molecular, genetic, and pharmacological studies have shown that neprilysin (also called NEP) catabolizes amyloid beta peptides (A beta) in healthy conditions. However, in Alzheimer disease (AD), A beta accumulates forming senile plaques in brain parenchyma and amyloid deposition around blood vessels. In this study, we tested at cellular level the relationship between neprilysin and A beta in human healthy and AD brain. Our results provided evidence for declining levels of neprilysin in AD brains as compared to healthy controls in parallel with increasing deposition of A beta. In hippocampus of AD individuals we observed a significant down-regulation of neprilysin expression in pyramidal neurons, consistent with the possibility that neprilysin controls the level of A beta accumulation and plaque formation in this area. In the cortex and leptomeninges, neprilysin was expressed in the smooth muscle cells of blood vessels. In sections from AD patients we observed a clear inverse relationship between neprilysin and A beta peptide levels in the vasculature, implicating neprilysin in cerebral amyloid angiopathy.
Carpentier
Mélanie
M
Département de biochimie, Faculté de médecine, Université de Montréal, Quebec, Canada.
Robitaille
Yves
Y
DesGroseillers
Luc
L
Boileau
Guy
G
Marcinkiewicz
Mieczyslaw
M
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000201:enzymology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D006624:Hippocampus / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology*; D015260:Neprilysin / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D015260:Neprilysin