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.
Cell-Permeable, Small-Molecule Activators of the Insulin-Degrading Enzyme
