Alzheimer’s clue found in specific plaque June 23, 2008

Researchers have uncovered a new clue to the cause of Alzheimer’s disease.

The brains of people with the memory-robbing form of dementia are cluttered with a plaque made up of beta-amyloid, a sticky protein. But there long has been a question whether this is a cause of the disease or a side effect. Also involved are tangles of a protein called tau; some scientists suspect this is the cause.

Now, researchers have caused Alzheimer’s symptoms in rats by injecting them with one particular form of beta-amyloid. Injections with other forms of beta-amyloid did not cause illness, which may explain why some people have beta-amyloid plaque in their brains but do not show disease symptoms.

The findings by a team led by Dr. Ganesh M. Shankar and Dr. Dennis J. Selkoe of Harvard Medical School are reported in the current online edition of the journal Nature Medicine.

The researchers used extracts from the brains of people who donated their bodies to medicine.

Forms of soluble beta-amyloid containing different numbers of molecules, as well as insoluble cores of the brain plaque, were injected into the brains of mice. There was no detectable effect from the insoluble plaque or the soluble one-molecule or three-molecule forms, the researchers found.

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• Nature Medicine: Current issue
• National Institute on Aging:  Research and info

But the two-molecule form of soluble beta-amyloid produced characteristics of Alzheimer’s in the rats, they reported.

Those rats had impaired memory function, especially for newly learned behaviors. Studies were also done on mice and when their brains were inspected, the density brain cells were reduced by 47 percent. The beta-amyloid seemed to affect synapses, the connections between cells that are essential for communication between them.

The research, for the first time, showed the effect of a particular type of beta-amyloid in the brain, said Dr. Marcelle Morrison-Bogorad, director of the division of neuroscience at the National Institute on Aging, which helped fund the research.

It was surprising that only one of the three types had an effect, she said in a telephone interview.

Morrison-Bogorad said the findings may help explain the discovery of plaque in the brains of people who do not develop dementia. For some time, doctors have wondered why they find some brains in autopsy that are heavily coated with beta-amyloid, but the person did not have Alzheimer’s.

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The answer may lie in the two types of beta-amyloid that did not cause symptoms.

Now, the question is why one has the damaging effect and not others.

“A lot of work needs to be done,” Morrison-Bogorad said. “Nature keeps sending us down paths that look straight at the beginning, but there are a lot of curves before we get to the end.”

Dr. Richard J. Hodes, director of the National Institute on Aging, said that “while more research is needed to replicate and extend these findings, this study has put yet one more piece into place in the puzzle that is Alzheimer’s.”

In addition to the Institute on Aging, the research was funded by Science Foundation Ireland, Wellcome Trust, the McKnight and Ellison foundations and the Lefler Small Grant Fund.

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Early Alzheimer’s patients pressing for research, resources June 6, 2008

Don Hayen has a handy way of deflecting the instant pity that comes when he reveals his Alzheimer’s disease: “But I haven’t lost my keys all day,” he quickly jokes.

Hayen is part of a growing new movement in Alzheimer’s: Patients whose disease is diagnosed early enough that they are still articulate and can demand better care and better research. They are giving a voice to a disease whose victims until now have remained largely silent, and powerless.

It’s a shift with big ramifications.

Alzheimer’s patients are joining their counterparts with cancer and HIV to lobby Congress for more money to hunt treatments. Some are advising top scientists to push for higher-stakes research even if it means higher risks. They’re even offering unprecedented glimpses into how a mind slowly unravels as they blog about their dementia.

“It’s labeled incurable and you end up being a vegetable. People think as soon as you’re labeled that way, you are. A lot of us aren’t,” says Hayen, 74, a retired San Diego, California, physician who joined about 30 other early stage Alzheimer’s patients last month for a lobbying blitz at the nation’s capital.

“I can still speak for those who can’t.”

More than 5 million Americans are estimated to be living with Alzheimer’s disease, although no one knows how many have been diagnosed. But research suggests as many as half of Alzheimer’s sufferers may be in the disease’s early stages. Doctors say they’ve begun diagnosing far more people who still have years of independent living ahead them than they did just a few years ago.

And this week, the Alzheimer’s Association begins pilot-testing a campaign in three cities — Richmond, Virginia; Minneapolis, Minnesota; and Oklahoma City, Oklahoma — aimed at increasing early diagnosis. “Know the signs — early detection matters,” advertising will urge.

Diagnosis can be difficult. There is no single test for dementia. Memory problems aren’t always even the obvious first symptom; Hayen cites unprovoked anger and disorientation.

Alzheimer’s Association: Info, resources

But early detection gives people a chance to plan for their future care while they still have the mental capacity to do so.

It also highlights some harsh unknowns. For example, do you medicate right away? Today’s drugs merely alleviate symptoms for a temporary period.

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Etanercept drug reverses early symptoms of Alzheimer’s in 10 minutes March 9, 2008

Scientists in the U.S. say a drug which can reverse some of the early symptoms of Alzheimer’s disease takes effect within 10 minutes.

The scientists from the University of California at Los Angeles, and the University of Southern California, say the memory of an 81-year-old man improved dramatically after the drug etanercept, currently used to treat arthritis, was injected into his spine.

Some studies have suggested that too much of a body chemical called tumour necrosis factor-alpha may be at least partly to blame for the advance of the condition.

Etanercept, which is licensed for use as a rheumatoid arthritis drug, works to block this body chemical.

The study highlights the importance of certain soluble proteins, called cytokines, in Alzheimer’s disease and the cytokine, tumor necrosis factor-alpha (TNF), is a critical component of the brain’s immune system.

In normal circumstances TNF finely regulates the transmission of neural impulses in the brain and the researchers hypothesized that elevated levels of TNF in Alzheimer’s disease interfere with this regulation.

The theory was that an injection of etanercept would reduce the elevated levels of TNF.

The scientists Dr. Edward Tobinick and Dr. Hyman Gross have already published a study which suggested that this could benefit Alzheimer’s patients.

They had noticed in previous research that injecting the drug into the neck spine seemed to deliver almost immediate effects.

The decided to test the medication on just one patient, a former doctor who had the early stages of the disease.

Before the injection they measured his performance on cognitive tests, and found he performed poorly and was unable to remember the name of the doctor treating him, the date, or the state in which he lived. Neither could he perform simple mental arithmetic, or name more than two animals.

To the astonishment of his family ten minutes after a dose of etanercept, he was noticeably calmer, more attentive, and less frustrated; he also knew he lived in California, knew the day of the week, and the month, could name five animals, and performed better at the arithmetic test.

His wife said he was clearer and more organized and his son declared the change immediately after the drug was administered was the “single most remarkable thing he had ever seen.”

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Perispinal Etanercept: Potential as an Alzheimer therapeutic March 9, 2008

I recently viewed a video that an Alzheimer’s patient has made extraordinary improvements in his cognitive skills and gait. You can view the video on www.alzheimersgroup.org. I am posting information that I locate on the drug Etanercept:

Each of the three patients I saw treated had been tested and diagnosed with probable Alzheimer’s disease by a neurologist before perispinal etanercept treatment had begun. They and their families invited me to be present during the treatment and in the interviews before and after. I noticed clinical improvement in each of the three patients within minutes following treatment. My first impression was that there was a clear, easily discernible, difference in each. They were more cheerful, more at ease, and more attentive. My impressions were the same as those shared by each of the families (please see the movie for example). This rapid turn around brought to mind the first time, now almost two decades ago[17], that I was the original witness to the remarkable overexpression of immune cytokines in activated glia in Alzheimer patients and even in fetuses and neonates with Down’s syndrome – I was amazed!

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