Study Pinpoints Alzheimer's Plaque Emergence Early and Deep in the Brain

A study published in Communications Biology has localized regions with the earliest emergence of amyloid plaque in the brain of a mouse model of Alzheimer's, and the level of plaque in one of those same areas of the human brain strongly correlates with the progression of the disease, reports Medical Xpress . The researchers determined amyloid starts taking root in deep brain regions like the mammillary body, the lateral septum, and the subiculum before traveling along specific brain circuits that ultimately lead to the hippocampus. The team used the SWITCH technology to label amyloid plaques and to clarify the brains of 5XFAD mice so that they could be visualized in fine detail at different ages. The researchers consistently observed initial plaque formation in deep brain structures and then migration along pathways like the Papez memory circuit to proliferate throughout the brain within six to 12 months. They confirmed in postmortem human brain tissue that if the mammillary body is an early point of plaque manifestation, then plaque density should grow in proportion with the disease's progress. "Thus we propose that amyloid-beta deposits start in susceptible subcortical structures and spread to increasingly complex memory and cognitive networks with age," the researchers concluded. The team also quantified the excitability of neurons in the mammillary body of 5XFAD mice and found them to be more excitable than similar mice that lacked the 5XFAD series of genetic alterations.