Alzheimer's, Dementia & Mental Health
Memories Return from Depths of Advanced Alzheimer’s
for Mice Given Neural Stem Cells
The stem cells secreted a protein causing new
neurites, strengthening and increasing the number of connections between
neurons - watch video
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Frank LaFerla, left, Mathew Blurton-Jones and
colleagues found that neural stem cells could be a potential treatment
for advanced Alzheimer's disease. Photo by Daniel A. Anderson,
University Communications |
July 27, 2009 – It is one of those things you might
wish for if given just one wish – the recovery of memory for those
suffering with advanced Alzheimer’s disease. Scientists at UC Irvine say
they have made it happen using neural stem cells with mice.
The mice, genetically engineered to have
Alzheimer's, performed markedly better on memory tests a month after
mouse neural stem cells were injected into their brains.
The stem cells
secreted a protein that created more neural connections, improving
cognitive function and raising hopes of a potential treatment for the
leading cause of dementia that afflicts 5.3 million people in the U.S.
"Essentially, the cells were producing fertilizer
for the brain," said Frank LaFerla, director of UCI's Institute for
Memory Impairments & Neurological Disorders, or UCI MIND, and co-author
of the study, which appears online the week of July 20 in the
Proceedings of the National Academy of Sciences.
Lead author Mathew Blurton-Jones, LaFerla and
colleagues worked with older mice predisposed to develop brains lesions
called plaques and tangles that are the hallmarks of Alzheimer's.
To learn how the stem cells worked, the scientists
examined the mouse brains. To their surprise, they discovered that just
6 percent of the stem cells had turned into neurons. (The majority
became the other two main types of brain cells, astrocytes and
oligodendrocytes.)
The stem cells didn't improve cognition by becoming
new neurons, nor did they act by reducing the number of plaques and
tangles.
Rather, the stem cells were found to have secreted
a protein called brain-derived neurotrophic factor, or BDNF. This caused
existing tissue to sprout new neurites, strengthening and increasing the
number of connections between neurons.
When the team selectively reduced BDNF from the
stem cells, the benefit was lost, providing strong evidence that BDNF is
critical to the effect of stem cells on memory and neuronal function.
"If you look at Alzheimer's, it's not the plaques
and tangles that correlate best with dementia; it's the loss of synapses
- connections between neurons," Blurton-Jones said.
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UCI Researchers
First to ID Beta Amyloid as AD Trigger
Frank LaFerla was
also principal investigator of a research project in 2005 that
claimed to be the first to discover that early beta amyloid
accumulation within neurons is the trigger for the onset of
memory decline in Alzheimer's.
Click to that news report in the SeniorJournal.com archives. |
"The neural stem cells were helping the brain form
new synapses and nursing the injured neurons back to health."
Diseased mice injected directly with BDNF also
improved cognitively but not as much as with the neural stem cells,
which provided a more long-term and consistent supply of the protein.
"This gives us a lot of hope that stem cells or a
product from them, such as BDNF, will be a useful treatment for
Alzheimer's," LaFerla said.
In April, LaFerla, Blurton-Jones and colleagues
were awarded $3.6 million by the California Institute for Regenerative
Medicine toward the development of an Alzheimer's therapy involving
human neural stem cells.
In addition to LaFerla and Blurton-Jones, Masashi
Kitazawa, Hilda Martinez-Coria, Nicholas Castello, Tritia Yamasaki,
Wayne Poon and Kim Green of UCI worked on the study, along with
Franz-Josef Muller and Jeanne Loring of the Scripps Research
Institute. Funding for the study was provided by the California
Institute for Regenerative Medicine and the National Institutes of
Health.
Initial report written by Jennifer Fitzenberger, University
Communications, UC Irvine
