Using LED lights flickering at a specific frequency, MIT researchers have shown that
they can substantially reduce the beta amyloid plaques seen in Alzheimer’s disease, in
the visual cortex of mice.
There are currently no effective therapies for Alzheimer's disease.
As lifespans increase and our population ages, Alzheimer's represents a looming public health
problem of immense proportions.
One that is also personal.
One in three adults in the United States will die from Alzheimer's, or age-related dementia,
touching almost everyone as a patient or a caregiver.
There are now 46 million people with Alzheimer's disease worldwide.
The total societal costs associated with dementia will reach $2 trillion by 2030.
Alzheimer's expenses are the greatest direct health care costs to the United States economy--
greater than cancer and heart disease.
New approaches to treat and reverse Alzheimer's disease are needed.
Recent studies suggest that Alzheimer's disease disrupts brain signaling and how neurons synchronize.
This specific type of neuron synchrony altered in Alzheimer's disease is called the gamma
rhythm.
Sensory information from our environment is critical to how the brain synchronizes and
communicates, which aids in our ability to remember loved ones names, recall what we
did last week, and to pay attention to where we put our car keys.
Altered gamma rhythms in Alzheimer's disease are due in part to the toxic accumulation
of a snipped protein called amyloid beta, resulting in fewer neurons firing in synchrony.
Research from the lab of Director Li-Huei Tsai of the Picower Institute for Learning
and Memory at MIT has sought to understand how Alzheimer's disease affects gamma rhythms
in the brain, under the premise that abnormal neuronal firing populations play a key role
in the symptoms of the disease.
First, Dr Tsai's team established that the gamma rhythm amplitude at the 40 Hertz range
was reduced in mice with Alzheimer's disease, called 5XFAD mice.
More specifically, the gamma rhythm was significantly decreased in a brain region crucial for learning
and memory-- the hippocampus.
The diminished gamma rhythm in 5XFAD mice occurred with the accumulation of amyloid
beta, which eventually becomes toxic and results in neuronal death and memory loss.
Next, researchers in her lab used optogenetics to artificially correct the gamma rhythm in
the hippocampus of 5XFAD Alzheimer's mice.
By stimulating neurons in the 40 Hertz range at the optimal gamma rhythm amplitude, Dr
Tsai's lab showed that amyloid beta levels were cut nearly in half.
Dr Tsai's discovered that the 40 Hertz optogenetic stimulation to correct the gamma rhythm in
Alzheimer's mice activated genes in brain cells called microglia.
Microglia are part of the brain's immune system and function in part to ingest or clear away
microorganisms that might cause disease.
Optogenetic stimulation at the 40 Hertz range activated microglia to promote the clearance
of amyloid beta.
To create an effective treatment in humans with Alzheimer's disease, it's ideal to invent
a non-invasive technique.
To this end, Li-Huei Tsai and her team created a sensory paradigm that uses flickering light
to restore the gamma rhythm and to reduce the levels of amyloid beta.
5XFAD Alzheimer's mice were exposed to 40 Hertz flickering light, which caused enhanced
gamma rhythm neuronal activity and reduced amyloid beta levels by over 50% in the visual
cortex.
In addition, the 40 Hertz flickering light treatment caused microglia in Alzheimer's
mice to become more active and dramatically increase in size by engulfing amyloid beta.
When the gamma flickering light treatment was used in older Alzheimer's mice with toxic
levels of amyloid beta, which results in aggregates called plaques, the plaques decreased.
However, for the plaque levels to remain low, the flickering light treatment had to be given
over several days versus hours.
This unique, non-invasive approach might lead to the development of treatments that can
affect the disease without the current pharmacological challenges of the blood brain barrier, or
unexpected drug interactions.
This technique is a big step in finding new and effective treatments for Alzheimer's disease
that one day may halt and reverse the symptoms of a disease that impacts so many of us.