The present study shows that prenatal to early postnatal treatment with the neurotrophic compound P021 in 3xTg-AD mice can not only prevent certain cognitive deficits, possibly in part via the increase in the activity of CREB and levels of glutamate receptors and rescue of PSD95 associated synaptic deficit, but also ameliorate selected pathological hallmarks, including Aβ plaque and tau pathologies and astrocyte-related markers of neuroinflammation. Here, CREB1 is linked to Alzheimer disease.