Scientists ID Brain Cells Most Vulnerable to Alzheimer's Disease

A study in Nature Neuroscience has for the first time specified the neurons in the brain most susceptible to Alzheimer's disease, reports Courthouse News Service . "Some cells end up with high levels of tau tangles well into the progression of the disease, but for some reason don't die," said University of California, San Francisco (UCSD) Professor Lea Grinberg. "It has become a pressing question for us to understand the specific factors that make some cells selectively vulnerable to Alzheimer's pathology, while other cells appear able to resist it for years, if not decades." The investigators identified the culprit neurons by analyzing the tissue of 10 donor brains from deceased individuals at different stages of the disease. These samples were subjected to complex single-nucleus RNA sequencing, which uncovered two groups of neurons that appeared to be early targets of Alzheimer's. The first group is in the entorhinal cortex, which governs memory, navigation, and perception of time, while the second is based within the superior frontal gyrus, associated with self-awareness. These two groups were linked by the production of the protein RORB, and further study confirmed that these neurons are not only highly vulnerable, but also attract more tau tangles than other groups. "Our discovery of a molecular identifier for these selectively vulnerable cells gives us the opportunity to study in detail exactly why they succumb to tau pathology, and what could be done to make them more resilient," said UCSD's Kun Leng.