Are cholinergic neurons “Patient Zero” of Alzheimer’s Disease?

In the hunt for the elusive origins of Alzheimer’s disease, researchers may have to dig deeper than ever before. Deeper into the brain, that is. According to a report in Nature Communications, the basal forebrain, a subcortical structure that houses cholinergic neurons, falls prey to neurodegeneration before the entorhinal cortex — the region commonly considered the disease’s first victim. Researchers led by Nathan Spreng of Cornell University in Ithaca, New York, tapped into longitudinal imaging, biomarker, and cognitive data from the Alzheimer’s Disease Neuroimaging Initiative to track the pathological chain of events leading to AD. They report that the forebrain had already started shriveling in people who had abnormal levels of Aβ42 in their cerebrospinal fluid but were still cognitively normal. In contrast, the entorhinal cortex only began to shrink once a person started having memory problems as well. Read more.