July 2018 Cell Reports paper out!

Alzheimer’s disease appears to spread throughout the brain as it progresses. How and why the disease spreads to some regions before others is a great mystery. Our paper provides a key insight into this mystery. Our findings suggest that the basal forebrain, a deep subcortical structure which contains virtually all of the brain’s cortically projecting cholinergic neurons, is particularly vulnerable to degeneration in Alzheimer’s disease. Critically, the basal forebrain’s cholinergic projections are not randomly organized. Specific subregions of the basal forebrain project to specific areas of the cortex – there is a topographic organization. As cholinergic neurons in specific areas of the basal forebrain degeneration, we hypothesized that their specific cortical targets might also degenerate due to loss of cholinergic input. We observed patterns of cortical degeneration consistent with this hypothesis, indicating that a loss of cholinergic input in the cortex may represent a key mechanism by which Alzheimer’s pathology ‘spreads’ in cortical areas. For more information, follow the link here