This study constructs a spatiotemporal single-nucleus transcriptomic atlas of neurons in the entorhinal cortex–hippocampal (EC-HPC) circuit during Alzheimer’s disease (AD) progression. By performing Smart-seq2-based single-nucleus RNA sequencing on neurons from APP/PS1 transgenic mice and wild-type controls across different brain regions and disease stages, the study reveals two distinct neuronal populations associated with AD pathology: progressively lost EC-stellate neurons and expanding GFAP⁺ neurons with glia-like features. These findings highlight neuronal identity changes and energy metabolism dysfunction in AD, offering new insights into early diagnosis and intervention.

Researchers at the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have developed a groundbreaking brain imaging technique that reveals how tiny blood vessels in the brain pulse with each heartbeat—changes that may hold clues to aging and diseases such as Alzheimer’s. The study, published in Nature Cardiovascular Research, introduces the first noninvasive method for measuring “microvascular volumetric pulsatility”—the rhythmic expansion and contraction of the brain’s smallest vessels—in living humans. Using ultra-high-field 7T magnetic resonance imaging (MRI), the team showed that these microvessel pulses increase with age, especially in the brain’s deep white matter, a region critical for communication between brain networks that is particularly susceptible as people age to reduced blood supply of distal arteries, the blood vessels that carry blood away from the heart and into the farthest parts of the body. Increasing microvessel pulses can disrupt systems in the brain, possibly speeding up memory loss and Alzheimer’s disease. The USC team’s innovation combines two advanced MRI approaches—vascular space occupancy (VASO) and arterial spin labeling (ASL)—to track subtle volume changes in microvessels over the cardiac cycle. The researchers confirmed that older adults show heightened microvascular pulsations in deep white matter compared to younger adults, and that hypertension further amplifies these changes.