Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease-like neuropathology.
Expression levels of amyloid beta (Abeta)-degrading enzymes, insulin degrading enzyme (IDE) and neprilysin (NEP), were examined in transgenic mice with Alzheimer's disease-like neuropathology. After the development of first Abeta plaques in transgenic mice brain, cortical mRNA and protein levels of IDE were significantly up-regulated in the transgenic mice compared to their non-transgenic littermates. Up-regulation of IDE mRNA-levels occurred in parallel with increased Abeta40 and Abeta42 production. Additionally, a significant positive correlation was observed between protein levels of IDE and full-length amyloid precursor protein (APP) in the cerebral cortex. mRNA and protein levels of NEP were also nominally up-regulated in Tg mice compared to controls. These data may reflect up-regulation of the IDE and possibly of NEP expression in response to the Abeta accumulation.
Vepsäläinen
Saila
S
Department of Neurology, University Hospital and University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland.
Hiltunen
Mikko
M
Helisalmi
Seppo
S
Wang
Jun
J
van Groen
Thomas
T
Tanila
Heikki
H
Soininen
Hilkka
H
D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D007339:Insulysin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D015260:Neprilysin; D007339:Insulysin