CREB1 and Alzheimer disease: Moreover, the TrkB/CREB pathway remained normal in 4–5-month-old 5XFAD mice, while Aβ-dependent suppression of CREB function has been reported in vitro54 and in advanced stages of AD mouse models, including 5XFAD at 8–9 months of age, in close association with their memory deficits.55, 56 Taken together, it seems likely that a combination of subthreshold levels of Aβ and dysfunctional TrkB due to heterozygous gene knockout may underlie deficient CREB signaling in TrkB+/–·5XFAD mice, consequently leading to the hippocampus-dependent memory impairments.