Early role of mitochondria in AD may help explain limitations to current beta amyloid hypothesis

Oct 13, 2010

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 -- 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 .

"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 in its earliest stages. One potential drug, cyclosporin, is already used in organ transplant and autoimmune patients. Cyclosporin suppresses the , 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, 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.

Explore further: US orders farms to report pig virus infections

add to favorites email to friend print save as pdf

Related Stories

Alzheimer's disease linked to mitochondrial damage

Apr 02, 2009

Investigators at Burnham Institute for Medical Research (Burnham) have demonstrated that attacks on the mitochondrial protein Drp1 by the free radical nitric oxide—which causes a chemical reaction called S-nitrosylation—mediates ...

Recommended for you

Filipino tests negative for Middle East virus

1 hour ago

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

US orders farms to report pig virus infections

Apr 18, 2014

The U.S. government is starting a new program to help monitor and possibly control the spread of a virus that has killed millions of pigs since showing up in the country last year.

Foreigner dies of MERS in Saudi

Apr 18, 2014

A foreigner has died after she contracted MERS in the Saudi capital, the health ministry said on announced Friday, bringing the nationwide death toll to 73.

Vietnam battles fatal measles outbreak

Apr 18, 2014

Vietnam is scrambling to contain a deadly outbreak of measles that has killed more than 100 people, mostly young children, and infected thousands more this year, the government said Friday.

New clues on tissue scarring in scleroderma

Apr 18, 2014

A discovery by Northwestern Medicine scientists could lead to potential new treatments for breaking the cycle of tissue scarring in people with scleroderma.

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.