The Effect of Curcumin on Aβ, Akt, and GSK3β on the Brain and Retina of APP/PS1 Mice and in the Blood of Alzheimer’s Patients with Early‑stage Disease

Background: Curcumin possesses multifunctional pharmacological properties, including antioxidant, anti‑inflammatory, and antidiabetic properties. We investigated whether curcumin can improve pathological changes associated with Alzheimer’s disease (AD), including amyloid β (Aβ), protein kinase B (PKB, also termed Akt), and glycogen synthase kinase 3β (GSK3β) levels and expression. Materials and Methods: Alzheimer’s transgenic APPSWE/ PS1ΔE9 mice and wild‑type mice were treated with curcumin by intragastric administration for 2 weeks at 2 and 5 months of age, respectively. Aβ plaques and contents in the brain and retina were measured by immunohistochemistry and enzyme‑linked immune sorbent assay, respectively, while the expression of Akt and GSK3β was tested by RNA isolation and quantitative real‑time polymerase chain reaction. Blood of patients with AD and age‑matched healthy controls was used to determine the contents of Aβ, Akt, and GSK3β. Results: Curcumin treatment decreased Aβ accumulation in the early stages of AD at 5 months (P < 0.001). It also improved AD‑associated pathological changes, including upregulation of Akt (P < 0.01) and downregulation of GSK3β (P < 0.01). In addition to AD‑associated changes, the proinflammatory cytokine interleukin (IL)‑1β was significantly decreased with curcumin treatment (P < 0.05). Conclusion: In the early stage of AD, curcumin can suppress Aβ accumulation, upregulate the expression of Akt, downregulate the expression of GSK3β, and inhibit the proinflammatory cytokine IL‑1β. But in the late stage, curcumin has an insignificant inhibitory effect on GSK3β. In patients with AD, a low expression of Akt and a high expression of GSK3β were observed. Curcumin may have a similar effect on patients with AD by regulating these protein expressions and can be used to improve the pathological features of AD in the early stages of the disease.