Featured Research

from universities, journals, and other organizations

Early role of mitochondria in Alzheimer's Disease may help explain limitations to current beta amyloid hypothesis

Date:
October 13, 2010
Source:
Columbia University Medical Center
Summary:
A new study in mouse models has found that the brain's mitochondria -- the powerhouses of the cell -- are one of the earliest casualties of the disease. The study also found that impaired mitochondria then injure the neurons' synapses, which are necessary for normal brain function.

Before Alzheimer's patients experience memory loss, the brain's neurons have already suffered harm for years.

A new study in mouse models by researchers at Columbia University Medical Center has found that the brain's mitochondria -- the powerhouses of the cell -- are one of the earliest casualties of the disease. The study, which appeared in the online Early Edition of PNAS, also found that impaired mitochondria then injure the neurons' synapses, which are necessary for normal brain function.

"The damage to synapses is one of the earliest events in Alzheimer's disease, but we haven't been able to work out the events that lead to the damage," says the study's principle investigator, ShiDu Yan, M.D., professor of clinical pathology and cell biology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center. "Our new findings, along with previous research, suggest that mitochondrial changes harm the synapses, and that we may be able to slow down Alzheimer's at a very early stage by improving mitochondrial function."

Drugs that restore mitochondria function may be able to treat Alzheimer's disease in its earliest stages. One potential drug, cyclosporin, is already used in organ transplant and autoimmune patients. Cyclosporin suppresses the immune system, but it also blocks amyloid beta (Aβ) peptides-induced mitochondrial injury, Dr. Yan has found in previous studies (Du et al. Nature Medicine, 2008).

Cyclosporin, however, has too many toxic side effects for long term use in other patients. Dr. Yan is currently trying to alter the chemical structure of the drug to reduce its toxicity and to improve its ability to cross the blood brain barrier but preserve its protective effect on Aβ-mediated toxicity.

Most Alzheimer's researchers initially believed that Aβ peptides caused the disease after aggregating together in large, extracellular plaques, a defining feature of Alzheimer's-affected brains. But Dr.Yan's findings, along with those of many other scientists, now point to an earlier role for Aβ peptides inside the brain's neurons.

The mitochondria are damaged, the researchers found, when (Aβ) peptides breach the mitochondria's walls and accumulate on the inside. Even low concentrations of Aβ peptides, equivalent to the levels found in cells years before symptoms appear, impair the mitochondria, particularly mitochondria that supply power to the neuron's synapses.

When filled with Aβ peptides, these synaptic mitochondria were unable to travel down the neurons' long axons to reach, and fuel, the synapse. And the mitochondria that did make the journey failed to provide adequate energy to operate the synapses. Without operating synapses, neurons are unable to function.

"Since cyclosporin is already FDA approved for use in organ transplant and autoimmune patients, this research has the potential to lead to more rapid clinical trials and progress quickly," said Dr. Yan.

Next, Dr. Yan and her team also plan to do more research on the role of tau, which like beta amyloid, is the protein associated most with the plaques and tangles seen at autopsy in the brains of those with Alzheimer's.

This work was supported in part by the National Institute on Aging (NIA) of the National Institutes of Health (NIH), and the Alzheimer's Association.

Authors of the paper are: Heng Du , Lan Guo, Shiqiang Yan, Alexander A. Sosunov, Guy M. McKhann, and Shirley ShiDu Yan.


Story Source:

The above story is based on materials provided by Columbia University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Columbia University Medical Center. "Early role of mitochondria in Alzheimer's Disease may help explain limitations to current beta amyloid hypothesis." ScienceDaily. ScienceDaily, 13 October 2010. <www.sciencedaily.com/releases/2010/10/101013122557.htm>.
Columbia University Medical Center. (2010, October 13). Early role of mitochondria in Alzheimer's Disease may help explain limitations to current beta amyloid hypothesis. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2010/10/101013122557.htm
Columbia University Medical Center. "Early role of mitochondria in Alzheimer's Disease may help explain limitations to current beta amyloid hypothesis." ScienceDaily. www.sciencedaily.com/releases/2010/10/101013122557.htm (accessed August 30, 2014).

Share This




More Mind & Brain News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Young Entrepreneurs Get $100,000, If They Quit School

Young Entrepreneurs Get $100,000, If They Quit School

AFP (Aug. 29, 2014) Twenty college-age students are getting 100,000 dollars from a Silicon Valley leader and a chance to live in San Francisco in order to work on the start-up project of their dreams, but they have to quit school first. Duration: 02:20 Video provided by AFP
Powered by NewsLook.com
Baby Babbling Might Lead To Faster Language Development

Baby Babbling Might Lead To Faster Language Development

Newsy (Aug. 29, 2014) A new study suggests babies develop language skills more quickly if their parents imitate the babies' sounds and expressions and talk to them often. Video provided by Newsy
Powered by NewsLook.com
Electrical Stimulation Boosts Brain Function, Study Says

Electrical Stimulation Boosts Brain Function, Study Says

Newsy (Aug. 29, 2014) Researchers found an improvement in memory and learning function in subjects who received electric pulses to their brains. Video provided by Newsy
Powered by NewsLook.com
Treadmill 'trips' May Reduce Falls for Elderly

Treadmill 'trips' May Reduce Falls for Elderly

AP (Aug. 28, 2014) Scientists are tripping the elderly on purpose in a Chicago lab in an effort to better prevent seniors from falling and injuring themselves in real life. (Aug.28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins