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.