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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 beta-amyloid (Abeta)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 Abeta from the brain.
Pubmed ID: 16769157
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A research center associated with the University of Pittsburgh that specializes in the diagnosis of Alzheimer's disease and related disorders. The overall objective of the ADRC is to study the pathophysiology of Alzheimer's disease, with the aim of improving the reliability of diagnosis of Alzheimer's and developing effective treatment strategies. Current research foci emphasize neuropsychiatry and neuropsychology, molecular genetics and epidemiology, basic neuroscience, and structural and functional imaging that aid in the diagnosis and treatment of Alzheimer's disease. Specific services at the ADRC include: comprehensive diagnostic evaluation of patients with suspected Alzheimer's disease and other forms of dementia; evaluation of memory, language, judgment, and other cognitive abilities; and education and counseling for patients and families.
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