Accumulation of BRI2-BRICHOS ectodomain correlates with a decreased clearance of Aβ by insulin degrading enzyme (IDE) in Alzheimer’s disease

2015 ◽  
Vol 589 ◽  
pp. 47-51 ◽  
Author(s):  
M. Del Campo ◽  
A. Stargardt ◽  
R. Veerhuis ◽  
E. Reits ◽  
C.E. Teunissen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

Substantial linkage disequilibrium across the insulin-degrading enzyme locus but no association with late-onset Alzheimer's disease

2001 ◽  
Vol 109 (6) ◽  
pp. 646-652 ◽  
Author(s):  
Richard Abraham ◽  
Amanda Myers ◽  
Fabienne Wavrant-DeVrieze ◽  
Marian L. Hamshere ◽  
Hollie V. Thomas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Linkage Disequilibrium ◽  
Late Onset ◽  
Enzyme Locus ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

P1-068: Cognitive phenotypes in Alzheimer's disease and insulin degrading enzyme gene variants

2010 ◽  
Vol 6 ◽  
pp. S193-S193
Author(s):  
Emma R.L.C. Vardy ◽  
Kristelle Brown ◽  
Cheryl L. Stopford ◽  
Noor Kalsheker ◽  
David Neary ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Variants ◽  
Insulin Degrading Enzyme ◽  
Enzyme Gene ◽  
Degrading Enzyme

P4-079 Is variation in the gene encoding insulin-degrading enzyme (IDE) a risk factor in late-onset Alzheimer's disease?

2004 ◽  
Vol 25 ◽  
pp. S496-S497
Author(s):  
Petra Nowotny ◽  
Scott Smemo ◽  
Tony Hinrichs ◽  
Peter Holmans ◽  
Kristina Tracey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Late Onset ◽  
Insulin Degrading Enzyme ◽  
Gene Encoding ◽  
Degrading Enzyme

scholarly journals Reduced Hippocampal Insulin-Degrading Enzyme in Late-Onset Alzheimer's Disease Is Associated with the Apolipoprotein E-ε4 Allele

2003 ◽  
Vol 162 (1) ◽  
pp. 313-319 ◽  
Author(s):  
David G. Cook ◽  
James B. Leverenz ◽  
Pamela J. McMillan ◽  
J. Jacob Kulstad ◽  
Sasha Ericksen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Ε4 Allele

scholarly journals Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Xin-Yi Lu ◽  
Shun Huang ◽  
Qu-Bo Chen ◽  
Dapeng Zhang ◽  
Wanyan Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Mrna Expression ◽  
Insulin Degrading Enzyme ◽  
Antidiabetic Drug ◽  
Degrading Enzyme ◽  
Expression Levels ◽  
The Brain ◽  
Mrna Expression Levels

Alzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.

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