Alterations to brain signalling and neuron synchronisation may lead people to develop Alzheimer's disease, by promoting the accumulation of protein amyloid-β in the brain. However, normal brain activity may be restored and amyloid plaques cleared by using a light-mediated technique.
As Alzheimer's disease progresses, brain tissues shrink, affecting the brain's structure and the function of key areas. Although it is not clear what causes this process to begin in the first place, abnormal protein deposits – amyloid plaques and tau tangles – are shown to accumulate and chemical imbalances have been identified in the brains of patients.
Additionally, studies have shown that Alzheimer brains also present desynchronised neural activity and a loss of oscillatory activity.
However, it is not known how these neural changes are linked to the biological changes that underlie disease progression, such as protein accumulation.
In this new study published in the journal Nature Neurology, scientists working on a mouse model have suggested that when a specific type of neuron synchrony known as gamma rhythm is altered, amyloid-β proteins begin to accumulate in the animals' brains.
Light to stimulate neurons
The team, led by Li-Huei Tsai from the MIT in the US, first recorded the neural activity of mutant mice with Alzheimer's disease. In their brains, gamma oscillations declined. This was then followed by amyloid-β accumulation and by the first signs of cognitive decline in the animals.
An optogenetic technique – a flickering light set at a specific frequency – was used to stimulate neurons in a part of the mice's brains closely associated with memory and learning and known as the hippocampus.
This technique led to the activation of microglia, the main immune cells in the central nervous system. The scientists also observed a decreased production of the protein amyloid-β, as it was cleared by microglia.
In order for these findings to be translated one day into the clinic, scientists have to come up with the least invasive technique possible. Here they have designed and tested a method which involved restoring gamma oscillations in the brain by flickering LED lights at a frequency of 40Hz. This reduced amyloid-β levels in the visual cortex of mice at early stages of Alzheimer's disease, and cleared a number of amyloid plaques at more advanced stages of the disease.
Because this approach is so different to all that have been tested so far, more research will be needed to assess the risks and the benefits of restoring gamma oscillations in the brain. We are a long way away from this technique being used as a therapy in human, but these findings open interesting new perspectives.