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Dysfunctional precursor protein impairs making of new neurons in brain.

Amyloid precursor protein (APP) modulates the many processes through which newborn neurons are generated in the adult brain, state researchers from Baylor College of Medicine in a new study. An important component of the proper formation of these neurons are the GABAergic interneurons, which maintain a state of homeostasis between excitation and inhibition.

When new neurons are generated from neural stem cells, they are first produced as precursor cells and then differentiate into neurons and other types of brain cells.  After the cells differentiate, they need to incorporate into the brain and existing networks of brain cells. Without functioning APP, the neurons do not form the proper morphology and cannot integrate into the existing networks. They die after they are generated.

To study the issue the team used a mouse model that allowed them to knock out APP in different kinds of neurons.

There were three possibilities for the researchers,  APP could be expressed within the new neurons or within the excitatory neurons or within inhibitory neurons.  When they inhibited APP in the three populations of neurons, they found that GABAergic interneurons modulate the neurogenesis or production of new neurons.

Inhibitory neurons play as important a role as excitatory neurons, although the latter are far more numerous.  Therefore, formation of new neurons or neurogenesis in adults decreases with age. This helps us understand why age is such a critical factor when speaking about Alzheimer’s disease.

Source:  Baylor College of Medicine

APP as a gene regulator.  The intracellular domain of APP can translocate into the nucleus upon secretase cleavage and activate transcription of target genes.  Credit:  University of Zurich.
APP as a gene regulator. The intracellular domain of APP can translocate into the nucleus upon secretase cleavage and activate transcription of target genes. Credit: University of Zurich.

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