Insulin-degrading enzyme protein level is lower in Alzheimer's disease patients

Objectives:
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. Therefore, this review article has been conducted.

Is there an association between insulin-degrading enzyme protein level and risk of Alzheimer's disease (AD)?

Study design:
This review article included 7 studies for IDE protein level (Alzheimer's disease cases = 293 and controls (persons without Alzheimer's disease)  = 126), 3 for mRNA level (Alzheimer's disease cases = 138 and controls = 81) and 3 for enzyme activity (Alzheimer's disease cases = 123 and controls = 75).

Results and conclusions:
The investigators found the insulin-degrading enzyme protein level was significantly lower in Alzheimer's disease patients than in controls [SMD = -0.47, 95% CI = -0.69 to -0.24, p 0.001].
But insulin-degrading enzyme mRNA and enzyme activity had no significant difference [SMD = 0.02, 95% CI = -0.40 to 0.43 and SMD = 0.06, 95% CI = -0.41 to 0.53, respectively].

The investigators found in subgroup analyses (to get more information) that insulin-degrading enzyme protein level was decreased in both cortex and hippocampus of Alzheimer's disease patients [SMD = -0.43, 95% CI = -0.71 to -0.16, p = 0.002 and SMD = -0.53, 95% CI = -0.91 to -0.15, p = 0.006 respectively].
However, insulin-degrading enzyme mRNA was higher in cortex of Alzheimer's disease patients [SMD = 0.71, 95% CI = 0.14 to 1.29, p = 0.01] but not in hippocampus [SMD = -0.26, 95% CI [= -0.58 to 0.06].

The investigators concluded that Alzheimer's disease patients have lower insulin-degrading enzyme protein level. Further relevant studies are still needed to verify whether insulin-degrading enzyme is one of the factors affecting Aβ abnormal accumulation and throw new insights for Alzheimer's disease detection or therapy.

Original title:
Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-analysis by Zhang H, Liu D, […], Zhou H.

Link:
https://www.ncbi.nlm.nih.gov/pubmed/29357797

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