Farris W, Mansourian S, Leissring MA, Eckman EA, Bertram L, Eckman CB, Tanzi RE, Selkoe DJ.
Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein.
Am J Pathol. 2004 Apr;164(4):1425-34.
Please login to recommend the paper.
To make a comment you must login or register.
As reported by Schmitz et al., IDE may be involved in degradation of Aβ transported from the inside of the ER to the cytoplasm, particularly under pathological conditions (1). However, I would urge caution in directly relating IDE mutations with AD through Aβ degradation for the following reasons.  Insulin and AICD (and quite likely some cytosolic peptides similar to AICD) are far better substrates than Aβ for IDE.  Insulin is known to alter APP processing through a distinct signal transduction mechanism (2,3). Therefore, it is very likely that the relationship between diabetes and AD can be accounted for primarily by altered insulin signaling.
Schmitz A, Schneider A, Kummer MP, Herzog V.
Endoplasmic reticulum-localized amyloid beta-peptide is degraded in the cytosol by two distinct degradation pathways.
Traffic. 2004 Feb;5(2):89-101.
Gasparini L, Gouras GK, Wang R, Gross RS, Beal MF, Greengard P, Xu H.
Insulin-regulated β-amyloid protein trafficking: Stimulated secretion and reduced intracellular accumulation of Aβ in neuronal cell cultures.
Neurobiology of Aging, May 2000, vol. 21, no. 1001, pp. 183-183(1).
Gasparini L, Netzer WJ, Greengard P, Xu H.
Does insulin dysfunction play a role in Alzheimer's disease?.
Trends Pharmacol Sci. 2002 Jun;23(6):288-93.