In a now popular video game, pugnacious birds are catapulted at jumbled debris, with the goal of liberating their entrapped comrades. Analogously, potentiation of the cognition-mediating transcriptional factor, cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), or its downstream effectors, may release memory or cognitive function fettered by Alzheimer's disease pathology.

AD accounts for 50–60% of all cases of dementia, and currently affects 25 million people worldwide. The initial symptoms are cognitive deficits in several domains, including memory, language, and perceptual skills. Gross neuropathological changes such as the formation of extracellular amyloid plaques, composed of β-amyloid (Aβ) aggregates, and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein are the molecular hallmarks of AD. Currently, there are no therapies to slow or otherwise halt the disruptions in neural communication that drive the progression of AD. Previous studies have linked Aβ to synaptic abnormalities and functional deficits associated with AD (Smith et al, 2009). Pathological aggregation of Aβ promotes synaptic dysfunction and disrupts activity-dependent gene transcription essential for learning and long-term memory formation. One such event in AD is the dysregulation of the transcription factor CREB. CREB signaling has a crucial role in orchestrating gene expression necessary for long-term synaptic plasticity and memory (Lopez de Armentia et al, 2007) and is highly conserved across species. Though the mechanisms underlying altered activity-dependent gene transcription in AD are largely unknown, selectively targeting CREB and its coactivators in AD patients presents a novel strategy for treating cognitive deficits. Inside this issue, Yiu et al, (2011) report the study of mice that express a human β APP695 transgene with familial AD mutations, resulting in Aβ pathology in the dorsal hippocampus characteristic of early-onset AD. These mice exhibited pronounced spatial memory impairment.

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