A link between amyloid-β (Aβ) deposition and α4β2 nicotinic acetylcholine receptor availability in specific brain regions could provide a clue to the mechanisms underlying cognitive decline in Alzheimer disease (AD), according to a new report. In patients with AD, Okada et al. found an inverse relationship between Aβ burden and α4β2 receptor availability in the nucleus basalis magnocellularis and medial frontal cortex, but not in other brain regions. This region-specific effect might explain why the global Aβ burden in the brain is often an unreliable indicator of cognitive function.