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Molecular mechanisms describe the Aβ-induced vicious circle. Aβ1-42 induces HPA axis hyperactivity and decreases the cAMP level, leading to abnormalities in downstream molecules, i.e., decreased phosphorylation of CREB and BDNF expression, which in turn to deteriorate learning and memory disorders. However, Inhibition of PDE4 increases cAMP level and stimulates HPA axis negative feedback regulation, resulting in decreases in CORT releasing and CRF receptor and GR expression.
