Scientists from the Riken Brain Science Institute in Japan report that the lack of autophagy in neurons prevents the secretion of amyloid beta and the formation of amyloid beta plaques in the brain. They believe their study not only sheds light on the metabolism of amyloid beta and its role in neurodegeneration and memory loss but that it indicates that autophagy, an important cellular auto-cleaning mechanism, might be a potential new drug target for the treatment of Alzheimer’s disease (AD).
The research team just published their study (“Aβ Secretion and Plaque Formation Depend on Autophagy”) based on work with transgenic mice in Cell Reports.
Autophagy is a cellular-cleaning mechanism that normally clears any protein aggregates or other “trash” within the cells, but that is somewhat disturbed in Alzheimer’s patients.
To investigate the role of autophagy in amyloid beta metabolism, Per Nilsson, Ph.D., and colleagues deleted an important gene for autophagy (Atg7) in a mouse model of Alzheimer’s disease. Contrary to what they were expecting, their results showed that a complete lack of autophagy within neurons prevents the formation of amyloid beta plaque around/outside the cells. Instead, the peptide accumulates inside the neurons, where it causes neuronal death, which in turn leads to memory loss.
“This reduction of Aβ plaque load was due to inhibition of Aβ secretion, which led to aberrant intraneuronal Aβ accumulation in the perinuclear region,” wrote the investigators. “Our results establish a function for autophagy in Aβ metabolism: Autophagy influences secretion of Aβ to the extracellular space and thereby directly affects Aβ plaque formation, a pathological hallmark of AD.”
According to Dr. Nilsson, “To control amyloid beta metabolism including its secretion is a key to controlling the disease. Autophagy might therefore be a potential drug target for the treatment of Alzheimer’s disease.”
