Insulin degrading enzyme activity selectively decreases in the hippocampal formation of cases at high risk to develop Alzheimer's disease

Abstract In this study we report that the membrane-bound, but not cytosolic insulin degrading enzyme (IDE) protein concentration and IDE activity are significantly decreased in the hippocampal formation of cases affected by mild cognitive impairment (MCI) which are at high risk to develop Alzheimer&...

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Bibliographic Details
Published in:Neurobiology of aging 2007-06, Vol.28 (6), p.824-830
Main Authors: Zhao, Zhong, Xiang, Zhongmin, Haroutunian, Vahram, Buxbaum, Joseph D, Stetka, Breton, Pasinetti, Giulio Maria
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alzheimer Disease - etiology
Alzheimer Disease - pathology
Amyloid beta-Peptides - metabolism
Analysis of Variance
CDR
Cell Membrane - enzymology
Cognition Disorders - complications
Cognition Disorders - pathology
Cytosol - enzymology
Entorhinal Cortex - metabolism
Female
Hippocampus - enzymology
Humans
IDE
Insulin - metabolism
Insulysin - metabolism
Internal Medicine
Iodine Isotopes - metabolism
Male
MCI
Neurology
Postmortem Changes
β-Amyloid
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Summary:Abstract In this study we report that the membrane-bound, but not cytosolic insulin degrading enzyme (IDE) protein concentration and IDE activity are significantly decreased in the hippocampal formation of cases affected by mild cognitive impairment (MCI) which are at high risk to develop Alzheimer's disease (AD), relative to normal neurological controls. Membrane-bound IDE protein concentrations and activity in the hippocampal formation continued to decrease during the conversion from MCI to mild–severe AD. This selective decrease in hippocampal membrane-bound, but not cytosolic, IDE concentration and activity was tissue specific since no changes in either membrane-bound or cytosolic IDE were found in the occipital cortex of the same cases examined. Most interestingly, the decreased hippocampal membrane-bound IDE protein activity negatively correlated with brain β-amyloid (Aβ)X-42 content in MCI and in AD brain. The study tentatively suggests that interventions aimed at promoting membrane-bound IDE activities in the brain of MCI cases may help to prevent the onset and possibly the progression into AD through mechanisms involving the clearance of monomeric Aβ from the brain.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2006.05.001