Does your brain shutdown with Alzheimer's?

June 12, 2002

FOR people with Alzheimer's disease, memories seem to leak away like the charge draining from a dying battery. The image is an apt one, because experiments on nerve cells suggest that as Alzheimer's takes hold, electrical charge may leak out of the brain cells, forcing them to "power down" and die, taking cherished memories with them.

The finding points to a new and unexpected mechanism for the way Alzheimer's disease damages the brain. And while the effect has yet to be demonstrated in living animals, there is tantalising evidence that drugs which block the effect could one day lead to new therapies for the condition.

Alzheimer's patients develop plaques in their brains when protein fragments called beta-amyloid clump together. When these plaques touch healthy brain cells, channels on the cell surface open up to let in a flood of calcium ions. This upsets the chemical balance of the cell, and it dies.

But it now turns out that another damaging process takes place that might help to kill off the cells. According to Vernon Ingram and a team at the Massachusetts Institute of Technology, the plaques appear to promote an additional flood of ions that destroys the potential difference that exists between the inside and the outside of a cell.

"Normal cells are negatively charged inside and positively charged on the outside," says Ingram. This potential difference across the cell membrane allows it to receive electrical signals from neighbouring cells. But Ingram's team found that when a plaque touches the cells, as well as positive calcium ions flooding in, negative chloride ions flow out, quickly draining the cell of its negative charge, just like a battery going dead.

Ingram, Barbara Blanchard and Veena Thomas added a special dye to cultures of human and rat nerve cells. The dye allows the researchers to measure the flow of ions, and hence the potential difference, across cell membranes. When they then added the amyloid peptide, the effect was dramatic: the cells became depolarised within minutes. "If this happens in memory-forming cells, you lose your memory," says Ingram.

Next, they exposed the depolarised cells to 1500 known drugs. The dye showed that 10 of the drugs reversed the depolarisation, restoring cells to normal. Some of these drugs are known to block channels that allow chloride ions to leave the cell, so an outward flow of chloride ions must be helping to depolarise the cell. Others blocked protein kinase C, an enzyme which may orchestrate the depolarisation from within the cell. The team now wants to test the drugs on brain slices from mice, and on live mice engineered to develop similar symptoms to Alzheimer's.

Richard Harvey, director of research at the Alzheimer's Society in London, is not convinced Ingram's group has hit on the key to Alzheimer's. "There's no evidence that membrane depolarisation is the most critical disease process," he says. "But I might be wrong." Neil Buckholtz, director of the dementias branch of the National Institute on Ageing in the US, says we need to know whether the drugs can actually cross the blood-brain barrier before any clinical trials.

Ingram agrees there's more to be done. "So far, we've only shown this in cell cultures," he says. "But it's a very promising first step and we're very excited about this."
-end-
Author: Andy Coghlan

More at: Biochemical and Biophysical Research Communications (vol 293, p 1197 and p 1204)

New Scientist issue: 15 JUNE 2002

PLEASE MENTION NEW SCIENTIST AS THE SOURCE OF THIS STORY AND, IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO: http://www.newscientist.com

"These articles are posted on this site to give advance access to other authorised media who may wish to quote extracts as part of fair dealing with this copyrighted material. Full attribution is required, and if publishing online a link to www.newscientist.com is also required. Advance permission is required before any and every reproduction of each article in full - please contact angela.bourton@rbi.co.uk. Please note that all material is copyright of Reed Business Information Limited and we reserve the right to take such action as we consider appropriate to protect such copyright."

New Scientist

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.