ScienceDaily (Aug. 21, 2012) — How abnormal protein deposits in the brains of Alzheimer’s patients disrupt the signalling between nerve cells has now been reported by researchers in Bochum and Munich, led by Dr. Thorsten Müller from the Medizinisches Proteom-Center of the Ruhr-Universität, in the journal Molecular and Cellular Proteomics. They varied the amount of APP protein and related proteins associated with Alzheimer’s disease in cell cultures, and then analysed how this manipulation affected other proteins in the cell. The result: the amount of APP present was related to the amount of an enzyme that is essential for the production of neurotransmitters and therefore for communication amongst nerve cells.

Mass spectrometer: The proteins are injected into the apparatus via a very thin needle. (Credit: © RUB-Pressestelle, Marion Nelle)

Proteomics: analysing all the proteins of the cells at once

Amyloid plaques are a characteristic feature of Alzheimer’s disease. They consist largely of cleavage products of the so-called amyloid precursor protein APP, which occur in excess in the brains of Alzheimer’s patients. What role APP plays in healthy people and why the abnormal accumulation of amyloid disrupts the regular functioning of the brain is still largely unclear. To understand the function of APP, the RUB researchers established a new cell model. The new cells produced only a very small amount of APP. What impact this had on all the other proteins of these cells was examined by the researchers through the use of mass spectrometry, among other things. With this method they identified over 2000 proteins and determined their concentrations. They were looking specifically for molecules whose concentrations in the newly established low-APP cells were different than in the reference cells that contained normal amounts of APP.

Abnormal protein able to curb neurotransmitter production

"One candidate has particularly caught our attention, this being the enzyme methionine adenosyltransferase II, alpha, MAT2A for short," Thorsten Müller said. Among other things, the enzyme is crucially involved in the production of neurotransmitters. Low-APP cells contained less MAT2A than the reference cells. To confirm the connection between the "Alzheimer’s protein" APP and the neurotransmitter-producing MAT2A, the team studied tissue samples from the brains of deceased Alzheimer’s patients and from healthy individuals. In the tissue of the Alzheimer’s patients there was less MAT2A than in the healthy samples. These results suggest that APP and MAT2A concentrations are related and are linked to the synthesis of neurotransmitters. "Our results point to a new mechanism by which the defective cleavage of the APP protein in Alzheimer’s disease could be directly related to altered neurotransmitter production," Müller said. "As a result, the signal transduction of nerve cells could be disrupted, which, over an extended period, could possibly also cause the death of cells."

Source: Science Daily

Aug. 20, 2012 by Quinn Eastman

People with Parkinson’s disease performed markedly better on a test of working memory after a night’s sleep, and sleep disorders can interfere with that benefit, researchers have shown.

The ability of sleep to improve scores on a test of working memory specifically depends on how much slow wave sleep Parkinson’s patients obtain, researchers have found.

While the classic symptoms of Parkinson’s disease include tremors and slow movements, Parkinson’s can also affect someone’s memory, including “working memory.” Working memory is defined as the ability to temporarily store and manipulate information, rather than simply repeat it. The use of working memory is important in planning, problem solving and independent living.

The findings underline the importance of addressing sleep disorders in the care of patients with Parkinson’s, and indicate that working memory capacity in patients with Parkinson’s potentially can be improved with training. The results also have implications for the biology of sleep and memory.

The results were published this week in the journal Brain.

"It was known already that sleep is beneficial for memory, but here, we’ve been able to analyze what aspects of sleep are required for the improvements in working memory performance," says postdoctoral fellow Michael Scullin, who is the first author of the paper. The senior author is Donald Bliwise, professor of neurology at Emory University School of Medicine.

The performance boost from sleep was linked with the amount of slow wave sleep, or the deepest stage of sleep. Several research groups have reported that slow wave sleep is important for synaptic plasticity, the ability of brain cells to reorganize and make new connections.

Sleep apnea, the disruption of sleep caused by obstruction of the airway, interfered with sleep’s effects on memory. Study participants who showed signs of sleep apnea, if it was severe enough to lower their blood oxygen levels for more than five minutes, did not see a working memory test boost.

In this study, participants took a “digit span test,” in which they had to repeat a list of numbers forward and backward. The test was conducted in an escalating fashion: the list grows incrementally until someone makes a mistake. Participants took the digit span test eight times during a 48-hour period, four during the first day and four during the second. In between, they slept.

Repeating numbers in the original order is a test of short-term memory, while repeating the numbers in reverse order is a test of working memory.

"Repeating the list in reverse order requires some effort to manipulate the numbers, not just spit them back out again," Scullin says. "It’s also a purely verbal test, which is important when working with a population that may have motor impairments."

54 study participants had Parkinson’s disease, and 10 had dementia with Lewy bodies: a more advanced condition, where patients may have hallucinations or fluctuating cognition as well as motor symptoms. Those who had dementia with Lewy bodies saw no working memory boost from the night’s rest. As expected, their  baseline level of performance was lower than the Parkinson’s group.

Participants with Parkinson’s who were taking dopamine-enhancing medications saw their performance on the digit span test jump up between the fourth and fifth test. On average, they could remember one more number backwards. The ability to repeat numbers backward improved, even though the ability to repeat numbers forward did not.

Patients needed to be taking dopamine-enhancing medications to see the most performance benefit from sleep. Patients not taking dopamine medications, even though they had generally had Parkinson’s for less time, did not experience as much of a performance benefit. This may reflect a role for dopamine, an important neurotransmitter, in memory.

Scullin and Bliwise are planning an expanded study of sleep and working memory, in healthy elderly people as well as patients with neurodegenerative diseases.

"Many elderly people go through a decline in how much slow wave sleep they experience, and this may be a significant contributor to working memory difficulties," Scullin says.

Source: Emory

20 August 2012 by Kayt Sukel

Some people can recall what happened on almost every day of their lives. Unlocking their secrets could shed light on the way all our memories work

IT WAS an email that memory researcher James McGaugh found hard to believe. The sender, a 34-year-old housewife named Jill Price, was claiming that she could recall key events on any date back to when she was about 12, as well as what she herself had done each day.

"Some people call me the human calendar," she wrote, "while others run out of the room in fear. But the one reaction I get from everyone who finds out about this ‘gift’ is amazement. I run my entire life through my head every day and it drives me crazy!"

McGaugh invited Price to his lab, making sure he had to hand a copy of 20th Century Day by Day, a book that lists important events by date. He opened the book to random pages and asked Price what had happened on those days. “Whether it was a plane crash or some elections or a movie star doing an outrageous thing, she was dead on,” he recalls. “Time and time again.”

That was in June 2000. McGaugh’s group has worked closely with Price ever since, and has discovered she is one of a select few with similar abilities. These individuals are neither autistic savants nor masters of mnemonic-based tricks of recall, yet they can remember key events from almost every day of their lives. Learning more about their abilities and how their brains are wired should lead to insights into the nature of human memory.

Intrigued by McGaugh’s findings, I arranged to visit his lab at the University of California, Irvine, to find out how these people live with such unusual abilities - and what it is like for the researchers working with them. “It never ceases to amaze me,” says McGaugh’s colleague, Aurora LePort. “Some of them can remember every day you give them.” She says studying people whose powers of recall seem to be enhanced, rather than impaired, offers us a new tool to explore memory.

It is certainly fair to say that most of our knowledge of memory derives from looking at memory loss. The classic case is that of Henry Molaison (better known as “HM”), who had surgery nearly 60 years ago to treat severe epilepsy. In a misguided attempt to remove the source of the seizures, several parts of the brain were cut out, including both hippocampi, curled up ridges on either side of the brain.

For HM, the consequences were catastrophic. Although he could still recall his early life, he was no longer able to lay down memories of things that happened to him after the surgery. Every day, the researchers studying his condition had to introduce themselves anew. Intriguingly, though, he could perform tasks that used short-term memory, like retaining a phone number for a few minutes.

Thanks to HM and many other people with neurological problems caused by head injuries and strokes, we now know that there are different kinds of remembering. Our short-term memories last up to about a minute, unless they are reinforced, or “rehearsed” through further repetition. While much about the neuroscience of memory remains mysterious, our hippocampi seem to be involved in turning these fleeting impressions into long-term memories, which are thought to be stored in the temporal lobes on either side of the brain.

Long-term memories can be subdivided into semantic ones to do with concepts, such as the fact that London is the UK capital, and autobiographical memories, about everyday events that we experience. Price has no special abilities with regard to her short-term or semantic memory, but when it comes to autobiographical memory, her scores are off the chart.

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