Discussion
The findings suggest that IDE and RCAN1 differentially modulate brain insulin signaling in relation to AD severity and ApoE genotype.
Methods
Temporal lobes from Long Evans rats treated with intracerebral streptozotocin or vehicle and postmortem frontal lobes from humans with normal aging AD (Braak 0-2), moderate (Braak 3-4) AD, or advanced (Braak 5-6) AD were used to measure IDE and RCAN mRNA and protein.
Results
Intracerebral streptozotocin significantly increased IDE and RCAN mRNA and protein. In humans with apolipoprotein E (ApoE) ε3/ε4 or ε4/ε4 and AD, IDE was elevated at Braak 3-4, but at Braak 5-6, IDE expression was significantly reduced. RCAN1 mRNA was similarly reduced in ApoE ε4+ patients with moderate or severe AD, whereas RCAN1 protein declined with the severity of AD and ApoE ε4 dose.