As people age, their muscles and joints often stiffen up, as do their brains. Dynamic modulation of brain activity—the activation and deactivation of networks in response to different cognitive challenges—diminishes with age and with Alzheimer’s disease, leading to poorer memory and other cognitive deficits. Now, a new study of healthy adults suggests that this happens faster in people who carry the apolipoprotein E4 (APOE4) allele, the strongest genetic risk factor for late-onset AD. The work, from Chris Foster, Karen Rodrigue, and Kristin Kennedy at the University of Texas at Dallas, appeared online June 26 in the Journal of Neuroscience.

The APOE4 allele increases the risk of age-related memory loss, accumulation of Aβ and amyloid, and thinning of the cerebral cortex and hippocampus. APOE4 also affects brain function. Normally, when the brain is at rest, activity hums along in a distributed set of brain regions called the default mode network. When faced with a job to do, such as remembering a bit of information, the brain dials down activity in default areas, and reallocates brainpower to regions needed for the task at hand. Aging, AD, and APOE4 all disrupt the shift, resulting in less deactivation where needed and worse learning and memory…