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.
