Light-based therapy for Alzheimer’s disease


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.

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