Scientists have identified the cells most susceptible to neurodegeneration in Alzheimer’s disease. In this respect informs Massachusetts Institute of Technology.
As Alzheimer’s disease progresses, neurodegeneration occurs with the accumulation of beta-amyloid plaques and misfolded tau proteins that form knots in the brain. One of the first areas of the brain to show neurodegeneration in Alzheimer’s disease is the mastoid body in the hypothalamus. However, for a long time it was unclear whether all neuron types were equally affected by the disease.
Mitchell Murdoch and his colleagues set out to find out. To do this, they performed RNA sequencing of brain cells and identified genes that act in different ways in different cell types. Using this approach, the researchers identified two main neuron populations, one in the medial mastoid and the other in the lateral mastoid. In lateral neurons, genes associated with synaptic activity were highly expressed and had a higher firing rate than medial mastoid neurons.
To elucidate the association of these neuron populations with Alzheimer’s disease, the authors experimented with genetically modified mice that developed the same disease at an early age. These mice appeared to have much more neuronal hyperactivity in the lateral mastoid body than healthy mice. At the same time, there was no difference in the activity of these two populations of neurons in healthy mice.
The researchers found that this hyperactivity occurs very early, around two months of age (the equivalent of a young adult), before amyloid plaques begin to develop. Lateral neurons became even more hyperactive as the mice aged, and also more susceptible to neurodegeneration than medial neurons. It is this hyperactivity that is associated with memory impairment and neuronal death.
However, experiments have shown that treatment of sick mice with levetiracetam can suppress hyperactivity and partially restore memory function. The authors hope that their discovery will continue towards preventing and even treating Alzheimer’s disease. This will greatly facilitate the life of patients, because in the severe form of Alzheimer’s disease, it leads to a complete loss of capacity and personality.
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