Scientists have now revealed one of the major toxic mechanisms of Alzheimer’s disease. This discovery could lead to a better understanding of the disease and better ways of treating it.
An enzyme is key to the AD mystery
The findings from The Scripps Research Institute (TSRI) show that brain damage in Alzheimer’s disease is linked to the over-activation of an enzyme called AMPK. When this enzyme is blocked in mouse models, neurons were protected from loss of synapses, a hallmark characteristic of early phase AD.
“These findings open up many new avenues of investigation, including the possibility of developing therapies that target the upstream mechanisms leading to AMPK over-activation in the brain,” explained TSRI Professor Franck Polleux, study lead researcher.
Lack of Alzheimer’s treatments creating crisis
Alzheimer’s disease is a fatal neurodegenerative disorder without effective treatments or a cure. The disease affects more than 25 million people worldwide, and the number is growing every year. The expense for treatment of those with the disease is projected to challenge the economies of countries worldwide.
From amyloid beta to AMPK to synaptic collapse
Researchers have long known that early-stage Alzheimer’s is characterized by synaptic loss in the memory centers of the brain. Small aggregates of amyloid beta can cause this loss, but the mechanism for the synaptic collapse has been a mystery.
Several studies came together to give Polleux and his team the idea to link discoveries in neuron research to recent discoveries in Alzheimer’s research. They decided to determine whether the reported interaction of AMPK with amyloid beta and tau can cause the type of damage found in Alzheimer’s patients’ brains.
“Very little was known about the function of this AMPK pathway in neurons, and we happened to have all the tools needed to study it,” said Polleux.
Polleux confirmed that amyloid beta does indeed strongly activate AMPK. They then showed that AMPK over-activation (by the amyloid beta) in the neurons is the essential reason for amyloid beta’s synapse-harming effect. They also discovered another enzyme, CAMKK2, which had a similar detrimental effect.
New treatments on the horizon
“We already have contacts within the pharmaceuticals industry who are potentially interested in targeting either CAMKK2 or AMPK,” noted Polleux.
Source: MedicalNewsToday, Neuron