Scientists identify strategies to protect new brain cells against Alzheimer's disease

December 3, 2009

Stimulating the growth of new neurons to replace those lost in Alzheimer's disease (AD) is an intriguing therapeutic possibility. But will the factors that cause AD allow the new neurons to thrive and function normally? Scientists at the Gladstone Institute of Neurological Disease (GIND) have discovered that two main causes of AD amyloid-beta (Aβ) peptides and apolipoprotein E4 (apoE4) impair the growth of new neurons born in adult brains. What is more, they have identified drug treatments that can normalize the development of these cells even in the presence of Aβ or apoE4. The findings are described in two separate papers published in the current issue of Cell Stem Cell.

Although it had long been assumed that cannot be renewed, it is now well established that new neurons are generated throughout the lives of mammals. One brain region in which new neurons are born in adults, the hippocampus, is involved in learning and memory and affected severely by Alzheimer's disease.

GIND investigator Li Gan, PhD, and her collaborators studied the development of neurons born in the hippocampus of adult mice genetically engineered to produce high levels of human Aβ in the brain. Surprisingly, Aβ initially accelerated the development of newborn neurons but then profoundly impaired their maturation at later stages of development.

"Interestingly," Dr. Gan said, "we were able to protect the newborn neurons and ensure their normal development with drugs that counteract Aβ-induced abnormalities in neural network activity. It is possible that these drugs could support the development of neurons from stem cells even in the hostile environment of the AD brain."

In a complementary study, GIND investigator Yadong Huang, MD, PhD and his team focused on apoE4, the major genetic risk factor for AD. The team used genetically engineered mice to study the effects of different human apoE variants on the maturation of neural stem cells or progenitor cells, from which new neurons develop in the adult brain. They found that apoE4 also impairs the development of new neurons in the hippocampus and identified drug treatments that could block these detrimental effects.

"Our findings suggest that apoE4 inhibits the development of newborn neurons by impairing specific signaling pathways and that boosting these pathways with drugs may be of therapeutic benefit," said Dr. Huang. "It might allow us to encourage the development of new neurons from to replace those lost in apoE4 carriers with AD."

"Although stem cell therapy for AD is still a long ways off, these studies have identified strategies to overcome major obstacles in the path towards this goal," said GIND Director Lennart Mucke, MD, who coauthored one of the studies. "They clearly demonstrate that drugs can be used to improve the development of newborn neurons in memory centers of the adult brain, even in the presence of toxic factors widely presumed to cause AD."

Source: Gladstone Institutes (news : web)

Explore further: Stem-cell therapies for brain more complicated than thought

Related Stories

New target for Alzheimer's disease identified

May 7, 2008

Alzheimer’s disease (AD) is an incurable disease that is increasing in prevalence and will increase even more rapidly as the Baby Boom generation enters the age of highest risk. The available AD drugs are only partially ...

Stem cells are good for the brain

July 15, 2008

For some years, scientists have been speculating over why stem cells exist in the brain, as brain regeneration is limited. A German team of neuroscientists believe these stem cells help keep the brain healthy and active.

Recommended for you

Ancient walnut forests linked to languages, trade routes

September 4, 2015

If Persian walnut trees could talk, they might tell of the numerous traders who moved along the Silk Roads' thousands of miles over thousands of years, carrying among their valuable merchandise the seeds that would turn into ...

Huddling rats behave as a 'super-organism'

September 3, 2015

Rodents huddle together when it is cold, they separate when it is warm, and at moderate temperatures they cycle between the warm center and the cold edges of the group. In a new study published in PLOS Computational Biology, ...

Fighting explosives pollution with plants

September 3, 2015

Biologists at the University of York have taken an important step in making it possible to clean millions of hectares of land contaminated by explosives.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.