A Network Explanation of Alzheimer's Regional Vulnerability

Studies in patients and mouse models have pinpointed a precise zone in the cerebral cortex selectively vulnerable to the earliest stages of Alzheimer's disease (AD): the borderzone covering the entorhinal and perirhinal cortical areas. An independent series of studies has revealed that this entorhinal-perirhinal borderzone is a central cortical hub, with a distinct connectivity pattern across the cerebral hemispheres. Here we develop a hypothesis that explains how this distinct network feature interacts with established pathogenic drivers of AD in explaining the disease's regional vulnerability and suggests how it acts as an anatomical source of disease spread.