Scientists have long been studying beta-amyloid, the sticky protein that builds up in the brains of those with Alzheimer’s disease. Everyone makes beta-amyloid, but in those with Alzheimer’s disease, the protein accumulates to toxic levels, eventually forming clumps in the brain called plaque that may play a part in damaging brain cells critical for thinking and memory.

But does this buildup of plaque occur in Alzheimer’s patients because they make too much beta-amyloid? Or are they unable to clear the sticky protein that naturally forms, the way healthy people do?

Researchers now have a better answer to these questions. It appears that those with Alzheimer’s make perfectly normal amounts of beta-amyloid. The problem is that they are unable to clear it from their brains.

“Clearance is impaired in Alzheimer’s disease,” said Dr. Randall Bateman, assistant professor of neurology at Washington University School of Medicine in St. Louis, who led the study that appeared in the journal Science. The findings could have important implications for diagnosis and treatment of Alzheimer’s, as researchers work to find treatments that can speed clearing of beta-amyloid from the brain.

In the study, researchers compared a group of 12 men and women with early Alzheimer’s disease with 12 healthy peers. Both groups produced beta-amyloid at the same average rate; the protein, at very low levels, seems to play an important role in keeping brain cells from becoming overexcited and firing abnormally. But compared to the healthy controls, those with early Alzheimer’s were 30 percent less able to clear the protein that accumulated in the brain.

The scientists estimate that over 10 years, enough beta-amyloid would accumulate in the brain to form the telltale plaques that damage brain areas crucial for thinking and memory.

“These findings may help point us toward better diagnostic tests and effective therapies. The next question is what is causing the decreased clearance rate,” Dr. Bateman said. “These findings support the idea that impaired beta-amyloid clearance is fundamentally linked to Alzheimer’s disease.”

Pathologists have long recognized beta-amyloid as a component of the plaques that riddle the brains of those with Alzheimer’s. One way the brain clears beta-amyloid is to move it into the spinal fluid, where it is broken down and disposed of. Understanding how this occurs could lead to new drugs and treatments that speed the process, before damage to the brain becomes extensive.

In those with Alzheimer’s, however, this process is impaired. Levels of beta-amyloid rise as the protein gets “stuck” in the brain, meaning that less of the substance moves into the spinal fluid. That’s one reason why studies have found that lower levels of beta-amyloid in the spinal fluid may be an early indicator of Alzheimer’s disease.

Many believe that accumulation of abnormal levels of beta-amyloid in the brain initiates a cascade of events leading to the death of brain cells and ultimately to dementia. In the rare, early-onset forms of Alzheimer’s that are linked to genetic mutations, there is a marked increase in beta-amyloid production. In the more common, late-onset form of Alzheimer’s, the mechanisms leading to increased beta-amyloid levels are not well understood.

Prior studies suggest several possible explanations for the slower clearance of beta-amyloid in late-onset Alzheimer’s. One possibility is that as beta-amyloid accumulates, it acts as a sink for more of the protein, trapping it within the brain. The researchers believe that sorting out these mechanisms is likely to help speed the development of new drugs for the disease.

“Abnormal protein deposits within the brain are a hallmark not only of Alzheimer’s disease, but of many neurological disorders. With knowledge about how these proteins accumulate, we may be able to slow that process and reduce the damage to the brain,” said Roderick Corriveau, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke.

Fisher Scientists Discover New Ways to Rid Cells of Alzheimer Protein, click here for full article.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source:

Kwasi G. Mawuenyega, Wendy Sigurdson, Vitaliy Ovod, et al: “Decreased Clearance of CNS Beta-Amyloid in Alzheimer’s Disease.” Science, published online December 9, 2010.

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High levels of high-density lipoprotein, or HDL, the so-called “good” cholesterol, appear to protect against Alzheimer’s disease, according to a new report. The findings come from a study of older adults living in New York City who were followed for about four years.

Previous studies have shown that high levels of HDL seem to protect against heart attacks and strokes. Hence the name “good” cholesterol. The new findings, publishing in the Archives of Neurology, from the American Medical Association, suggest HDL has protective effects, not just for the heart, but for the brain as well.

In the study, researchers at Columbia University’s Taub Institute for Research on Alzheimer’s and the Aging Brain studied 1,130 seniors living in northern Manhattan. None had Alzheimer’s at the start of the study. All were given blood tests to assess their cholesterol levels, including levels of HDL.

During the follow-up period, 101 of the participants developed Alzheimer’s; their average age was 83. Men and women who had the highest HDL levels, measuring 55 milligrams per deciliter of blood or higher, developed 60 percent fewer cases of Alzheimer’s disease than those with the lowest HDL levels, of 38 milligrams or less. The protective effect persisted even after the researchers considered such Alzheimer’s risk factors as age, education levels and genes that predispose to the disease.

Professional medical guidelines recommend that men raise HDL levels that are under 40 milligrams per deciliter, and that women increase HDL numbers under 50 milligrams. An HDL of 60 milligrams or higher is considered optimal.

Regular exercise, and especially aerobic activities like walking, dancing or running, are thought to boost levels of “good” HDL cholesterol. Other studies have shown that regular exercise may likewise reduce the risk of developing Alzheimer’s later in life. Exercise also improves cardiovascular function, including blood flow to the brain. In addition, a heart-healthy Mediterranean diet, rich in fish, nuts and healthy oils like olive oil, is also recommended to keep the brain healthy into old age.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source:

Christiane Reitz; Ming-Xin Tang; Nicole Schupf; Jennifer J. Manly; Richard Mayeux; José A. Luchsinger: “Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease.” Archives of Neurology, Vol. 67 (No. 12), pages 1491-1497.

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Every year, some 750,000 Americans suffer from sepsis, a life-threatening ailment that many have never heard of. The condition, sometimes called “blood poisoning” though no poison is involved, is an inflammatory response to serious infection that can cause damage to multiple tissues and organs. New findings show that the condition may lead to loss of memory and thinking skills that, when severe, may mimic the symptoms of Alzheimer’s disease.

Earlier this year, a study from the University of Washington in Seattle found that older men and women who receive critical care in the hospital are more likely to suffer from memory loss and cognitive decline than their peers who are not hospitalized and an earlier study, led by researchers at Beth Israel Deaconess Medical Center and Hebrew Senior Life in Boston, found that an episode of delirium, marked by agitation, confusion and hallucinations, rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients.

In the current study, researchers at the University of Michigan Medical School in Ann Arbor sifted through data from more than 27,000 men and women over 50 who were part of the Health and Retirement Study, an ongoing national health survey of American residents. Among the study participants, nearly 1,200 had been hospitalized for severe sepsis, a critical condition that requires intensive medical care and that can damage the skin, kidneys, lungs and other organs.

The researchers followed the sepsis patients for up to eight years and found that the condition was not just bad for the body. Many of those who had severe sepsis showed thinking and memory problems that were similar to those of Alzheimer’s and other forms of dementia.

“An episode of severe sepsis, even when survived, may represent a sentinel event in the lives of patients and their families, resulting in new and often persistent disability, in some cases even resembling dementia,” the authors wrote.

The researchers found that the prevalence of moderate to severe cognitive impairment increased 10.6 percentage points among patients who survived severe sepsis. Their odds of acquiring moderate to severe cognitive impairment were more than three times higher than those who didn’t have sepsis, including those who were admitted to the hospital for other medical problems.

“Cognitive and functional declines of the magnitude seen after severe sepsis are associated with significant increases in caregiver time, nursing home admission, depression, and mortality,” the authors wrote. “These data argue that the burden of sepsis survivorship is a substantial, under-recognized public health problem with major implications for patients, families and the health care system.” The study was published in the Journal of the American Medical Association.

The authors added that given published dementia and sepsis incidence rates for those ages 65 years or older in the United Slates, their results suggest that nearly 20,000 new cases per year of moderate to severe cognitive impairment in the elderly may be attributable to sepsis.

Unlike Alzheimer’s, sepsis is a curable condition, though it remains a leading cause of death in hospitals. Symptoms include fever, chills, difficulty breathing and general weakness. The condition can rapidly worsen, making immediate hospitalization and prompt treatment with fluids and antibiotics critical.

The findings point to the need for prompt medical care for serious infections in those with or without Alzheimer’s disease. They also point to the need for long-term follow-up, since even if the infection is successfully treated, there may be long-term damage to the brain and body.

In an editorial accompanying the study, Dr. Derek Angus of the University of Pittsburgh School of Medicine noted that the findings “…can help physicians when assessing care options and discussing outcomes with patients and families.” Researchers aren’t sure why sepsis may contribute to cognitive decline, but by raising awareness of the issue, the hope is that doctors and family members will be more aware of the risk of thinking and memory problems during and after hospital stays.

A trip to the hospital, with its strange sights and sounds and change in routine, can lead to confusion and agitation in any patient. The problem may be especially challenging for someone with Alzheimer’s disease. If hospitalization is needed, experts recommend that family members and loved ones stick close by whenever possible to help ease the transition.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source:

Theodore J. Iwashyna; E. Wesley Ely; Dylan M. Smith; et al.  “Long-term Cognitive Impairment and Functional Disability Among Survivors of Severe Sepsis.” Journal of the American Medical Association, Vol. 304(16), Oct. 27, 2010, pages 1787-1794.

Derek C. Angus: “The Lingering Consequences of Sepsis: A Hidden Public Health Disease?” Journal of the American Medical Association, Vol. 304(16), Oct. 27, 2010, pages 1833-1834.

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