Stem cells fertilize brains of Alzheimer’s mice

UC IRVINE (US)—Scientists have shown for the first time that neural stem cells can rescue memory in mice with advanced Alzheimer’s disease, suggesting a potential treatment for the leading cause of elderly dementia that afflicts 5.3 million people in the United  States.

Working with older mice predisposed to develop brain lesions called plaques and tangles that are the hallmarks of Alzheimer’s, researchers at the University of California-Irvine found that mice 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.

“Essentially, the cells were producing fertilizer for the brain,” explains study coauthor Frank LaFerla, director of the Institute for Memory Impairments and Neurological Disorders, or UCI MIND.

When they examined the mouse brains, the researchers found that the injected stem cells didn’t improve cognition by becoming new neurons or by reducing the number of plaques and tangles, but by secreting a protein called brain-derived neurotrophic factor, or BDNF, which in turn caused existing tissue to grow 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 it 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,” lead author Mathew Blurton-Jones explains. “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 says.

Researchers at the Scripps Research Institute contributed to the study, which was funded by the California Institute for Regenerative Medicine and the National Institutes of Health. The study appears online the week of July 20 in the Proceedings of the National Academy of Sciences.

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