ArticleJournal of Alzheimer's disease : JAD2012
Characterization of insulin degrading enzyme and other amyloid-β degrading proteases in human serum: a role in Alzheimer's disease?
Article in Journal of Alzheimer's disease : JAD, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Prediction Model for Mild Cognitive Impairment in Older Chinese Patients With Cerebral Small Vessel Disease Based on XGBoost Algorithms and Shapley Additive Explanations.CNS neuroscience & therapeutics · 2026Article
- Genetic and clinical investigation of insulin-degrading enzyme in Parkinson's disease within the Chinese Han population.Frontiers in neuroscience · 2026Article
- Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer's Disease.Neurology international · 2023Review
- Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases.Experimental neurobiology · 2023Review
- Medium-Chain Length Fatty Acids Enhance Aβ Degradation by Affecting Insulin-Degrading Enzyme.Cells · 2021Article
- Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme.ChemMedChem · 2021Article
- Heart and Brain: Complex Relationships for Left Ventricular Dysfunction.Current cardiology reports · 2020Review
- Ex vivoMolecular neurodegeneration · 2017Article
- Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.Neurobiology of aging · 2016Article
- Dual Exosite-binding Inhibitors of Insulin-degrading Enzyme Challenge Its Role as the Primary Mediator of Insulin Clearance in Vivo.The Journal of biological chemistry · 2015Article
- Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects.Neurobiology of aging · 2014Article
- Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2014Observational
- Biomarkers in amyloid-β immunotherapy trials in Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Review
- The association between small vessel infarcts and the activities of amyloid-β peptide degrading proteases in apolipoprotein E4 allele carriers.Angiology · 2013Article
- Blood-brain barrier transport of amyloid beta peptides in efflux pump knock-out animals evaluated by in vivo optical imaging.Fluids and barriers of the CNS · 2013Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Sporadic Alzheimer's disease (AD) patients have low amyloid-β peptide (Aβ) clearance in the central nervous system. The peripheral Aβ clearance may also be important but its role in AD remains unclear. We aimed to study the Aβ degrading proteases including insulin degrading enzyme (IDE), angiotensin converting enzyme (ACE) and others in blood. Using the fluorogenic substrate V (a substrate of IDE and other metalloproteases), we showed that human serum degraded the substrate V, and the activity was inhibited by adding increasing dose of Aβ. The existence of IDE activity was demonstrated by the inhibition of insulin, amylin, or EDTA, and further confirmed by immunocapture of IDE using monoclonal antibodies. The involvement of ACE was indicated by the ability of the ACE inhibitor, lisinopril, to inhibit the substrate V degradation. To test the variations of substrate V degradation in humans, we used serum samples from a homebound elderly population with cognitive diagnoses. Compared with the elderly who had normal cognition, those with probable AD and amnestic mild cognitive impairment (amnestic MCI) had lower peptidase activities. Probable AD or amnestic MCI as an outcome remained negatively associated with serum substrate V degradation activity after adjusting for the confounders. The elderly with probable AD had lower serum substrate V degradation activity compared with those who had vascular dementia. The blood proteases mediating Aβ degradation may be important for the AD pathogenesis. More studies are needed to specify each Aβ degrading protease in blood as a useful biomarker and a possible treatment target for AD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.