Feb 15/06:-  Exercise may offset the increased risk of Alzheimer's disease that comes with long-term use of pharmaceutical hormone replacement therapy (HRT), according to a new study.

OR...you could reduce your Alzheimer's risk even more by exercising AND avoiding long-term use of synthetic HRT.

My how times have changed. There was a moment - back in the early days of synthetic HRT - when researchers believed this therapy helped prevent breast cancer, heart disease and Alzheimer's. In recent years, however, studies have associated HRT use with an INCREASED risk of those diseases.

But HRT is still around - still prescribed by many doctors and still used by many women - even though there are safe alternatives, such as balancing menopausal hormone changes with bioidentical hormones. (See the e-Alert "Where's the Shame?" (2/7/06) for details about bioidentical hormones and how executives for Wyeth Pharmaceuticals have taken steps to obstruct women's right to choose this safer therapy.)

In this new study, just published in the journal Neurobiology of Aging, researchers investigated 54 menopausal women who used HRT for more than 10 years. This usage was associated with poorer mental acuity test scores and a reduction in tissue volume in several areas of the brain. But these negative effects were reduced among women with higher fitness levels.

To Your Good Health, Jenny Thompson, www.hsibaltimore.com
 

Could Green Tea be Good for Fighting Alzheimer's?
 
 
 Researchers have found that a component of green tea may protect the brain from Alzheimer's disease.

Epigallocatechin-3-gallate (EGCG) is a major antioxidant in green tea that has been widely studied for its reported protection against certain cancers. Now there is also evidence that EGCG decreases production of the protein beta-amyloid, which is related to Alzheimer's and can accumulate abnormally in the brain, leading to nerve damage and memory loss.

Scientists gave injections of pure EGCG to mice genetically programmed to develop Alzheimer's. There was an observed decrease of as much as 54 percent of the brain-clogging Alzheimer's plaques.

However, they also discovered that other flavonoids found in green tea may work against EGCG's ability to prevent beta-amyloid buildup, so drinking green tea alone may be insufficient. In addition, the amount of EGCG a patient needs to fight Alzheimer's is much higher than that found in green tea.

 Sources:
 The Journal of Neuroscience September 21, 2005; 25 (38): 8807-8814

Science Blog September 21, 2005
Reported by :   http://www.mercola.com/2005/oct/8/could_green_tea_be_good_for_fighting_alzheimers.htm

March 28, 2006:-   An HSI member named Jim has a question about Alzheimer's disease: "Is there anything you recommend that helps prevent Alzheimer's disease or will stabilize it or hold it at bay once it begins?"

Some sage might help.

In 2003, a team from Roozbeh Psychiatric Hospital in Tehran tested 42 elderly patients with mild to moderate AD. Half of the subjects received a daily dose of sage extract for 16 weeks. The researchers found that sage was effective in managing moderate symptoms of the disease while also reducing agitation.

For hundreds of years herbalists have known that sage is useful for improving the memory. The key is an enzyme called acetylcholinesterase (AChE), which breaks down a chemical called acetylcholine that is typically deficient in Alzheimer's patients. Researchers from the Medical Plant Research Centre (MPRC) at the Universities of Newcastle and Northumbria in the UK have shown that sage inhibits AChE.

Elaine Perry is the director of the MPRC. She and her colleagues have studied sage and other botanicals in the treatment of Alzheimer's. In 2004 she presented preliminary data that showed sage to have a significant effect on behavior and attention in healthy subjects. And when lemon balm was added to sage, the combination improved memory and mood.

Professor Perry also told Reuters Health: "Lemon balm reduced agitation and improved quality of life in people with Alzheimer's disease."

To Your Good Health, Jenny Thompson

Sources:

"Adults Listen Longer, But Teens Turn the Volume Up Higher" Miranda, Hitti, WebMD Medical News, 3/16/06, webmd.com
"Melatonin Pills May Help Ease Tinnitus" Miranda Hitti, WebMD Medical News, 2/24/06, webmd.com
"Plant Extracts May Ease Dementia Symptoms" Reuters Health, 3/5/04, reutershealth.com

Finding an Alzheimer's Switch:

An Unsuspected Protein Regulates the Production of Plaque-Forming Peptides

ProHealthNetwork.com   05-23-2005

BERKELEY, CA �?Researchers at the Department of Energy's Lawrence Berkeley National Laboratory have discovered an unsuspected subunit of the protein complex gamma-secretase, which plays a central role in Alzheimer's disease. The researchers have shown that the newly discovered component, the protein CD147, regulates the production of the toxic peptides that cause amyloid plaques, the brain lesions that are the defining feature of Alzheimer's.
"Alzheimer's is worse than a disease �?it takes the soul of a human being," says Bing Jap of Berkeley Lab's Life Sciences Division, in whose laboratory the new component was identified. "As the population of this country ages, the incidence of Alzheimer's is increasing, at a terrible increase in cost to society. Research leading to prevention or treatment is urgent."

The discovery and role of CD147 as a subunit of gamma-secretase by Jap and his colleagues Shuxia Zhou, Hua Zhou, and Peter Walian is reported in Proceedings of the National Academy of Sciences, in an article now in the online early edition of PNAS at http://www.pnas.org/cgi/content/abstract/0502768102v1?etoc.

How Alzheimer's works

The most persuasive hypothesis of how Alzheimer's disease invades the brain is the so-called "amyloid beta protein cascade," in which a protein called APP is clipped into shorter pieces by enzymes known as secretases. (APP stands for "amyloid precursor protein"; it is found in many tissues besides brain, but its functions are largely unknown.) If the portion of APP clipped by the beta form of secretase is further clipped by a third form, gamma secretase, the resulting fragments are amyloid beta peptides, A-beta 40 and A-beta 42. A-beta 42 in particular is toxic and causes the formation of amyloid plaques.

Unlike the majority of membrane proteins, gamma-secretase performs its proteolytic function neither inside nor outside the cell; instead, the crucial cut is made within the cell's thin membrane. In fact all the proteins and protein complexes involved �?APP and the alpha, beta, and gamma secretases �?are cell-membrane proteins, which penetrate the walls of the brain's neural cells. Alzheimer's research would greatly benefit if their structures, particularly that of gamma-secretase, could be established at high resolution by x-ray crystallography.

But membrane protein structures are particularly difficult to obtain. "Membrane protein complexes can be very difficult to purify in an intact form," says Jap. "Moreover, it's extremely difficult to get enough pure membrane protein to crystallize." Nevertheless Jap's laboratory has earned a reputation for solving the structures of important membrane proteins.

As the first step to producing enough gamma-secretase to make crystals, Jap asked postdoctoral fellow Shuxia Zhou to lead the effort to characterize the native protein complex. Zhou is a biochemist with M.D. and Ph.D. degrees from Shanghai Medical University; before coming to Berkeley Lab she studied and taught in Shanghai and at Oxford University and Kyoto University.

"Previous experiments establishing the role of gamma-secretase were genetic experiments done by causing its overexpression in cell lines and animal models," Zhou explains. "We wanted to isolate the native form and purify the whole gamma-secretase complex."

An unexpected factor

Zhou and her colleagues isolated the native complex from cells of the HeLa line and separated its subunits by gel electrophoresis, which pulls the components apart according to their molecular weights.

"There were six strong bands in the gel, five of which we could identify because we expected to find them," says Zhou. The expected bands represented the four known subunits of gamma-secretase, the proteins named Nct (nicastrin), APH-1 (anterior pharynx defective 1), PEN-2 (presenilin enhancer protein 2), and Psn-1 (presinilin 1) �?which is cleaved into two parts in the mature complex, Psn-1 NTF (the N-terminal fragment) and Psn-1 CTF (the C-terminal fragment). In prior Alzheimer's investigations, complexes made up of just these four components were shown to be an enzymatically active form of gamma-secretase, but whether they constituted the native form was not known.

From the evidence of gel electrophoresis, apparently not: "In addition to these five bands we found an extra band," Zhou says. "We didn't know what it was." To find out, she and her colleagues clipped the band from the gel, extracted the protein, and sequenced its amino acids.

The mystery protein turned out to be the membrane protein CD147. CD147 is expressed in many tissues and has many biological functions besides its role in tumor invasion, including reproduction, inflammation, and protein transport and sorting within cells. It also has a role in neural function: when the CD147 gene is deleted in mice, the result is defective nervous system development, loss of working memory, spatial learning deficits, and disorientation �?behaviors remarkably suggestive of Alzheimer's disease.

To investigate CD147's part in the activity of gamma-secretase, the researchers used targeted RNA to silence CD147 in cell cultures. The four previously known components of the gamma-secretase complex, as well as the APP protein on which they operate, were unaffected by this silencing. But when CD147 was silenced, the production of amyloid beta peptides increased markedly.

The researchers established that the native form of gamma-secretase, incorporating CD147, appears in other cell lines, including kidney cells and neuronal cells, and is not unique to HeLa cells (which are derived from cervical cancer). CD147 itself is found in many contexts besides gamma-secretase, but only as a part of gamma-secretase does it regulate the production of A-beta peptides and thus amyloid plaques.

Goals for further research

Just how does CD147 do what appears to be its normal job of preventing excessive production of A-beta 42 peptides, and what causes it to fail? Zhou says, "We know CD147 is a regulatory subunit of gamma-secretase, but we don't know how it works. As yet we don't know its mode of action with respect to the other members of gamma-secretase and its substrates. Determining this mode of action is a key goal of our future efforts."

About 25 amino-acid residues make up the length of CD147 that crosses through the cell membrane, one of which, glutamic acid, has net electrical charge. Such an unlikely placement for a charged residue suggests that this region of CD147 may seek to align with another protein's oppositely charged region, perhaps that of Psn-1.

Disruption of this transmembrane teamwork could lead to increased production of amyloid beta peptides which, in turn, may result in the amyloid beta plaque formation that is a hallmark of Alzheimer’s disease.

"The answer to how the components of gamma-secretase components fit together inside the cell membrane has to wait for high-resolution structural work," says Zhou, "and for that we first have to make enough of the native complex to make crystals."

Bing Jap adds, "Determining the atomic structure of the gamma-secretase complex, including CD147, is the next crucial step in understanding the molecular mechanisms by which the substrates are cleaved in various forms �?and the next crucial step to designing Alzheimer's disease therapeutics."

"CD147 is a regulatory subunit of the ?-secretase complex in Alzheimer's disease amyloid ß-peptide production," by Shuxia Zhou, Hua Zhou, Peter J. Walian, and Bing K. Jap, appears in the online early edition of the Proceedings of the National Academy of Sciences, http://www.pnas.org/cgi/content/abstract/0502768102v1?etoc.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at http://www.lbl.gov.

Contact: Paul Preuss, [email protected]

Chinese Scientists Isolate

Potential Cause of Alzheimer

A century after German doctor Alois Alzheimer (1864-1915) described the first documented case of Alzheimer's disease -- a serious cognitive decline suffered by elderly patients -- Chinese scientists may have discovered one of the illness' hidden facets. Their discovery reveals one more piece of the puzzle on this mysterious affliction, which affects millions worldwide.

The most striking early symptom of Alzheimer's is short-term memory loss, oft seen first as minor forgetfulness that worsens along with the illness, with a tendency to preserve older memories. As the disorder progresses, intellectual losses spread to language, movement co-ordination and recognition. When we know these abilities are seen as essential for quality of living, one can see the true devastating effect Alzheimer's disease has upon both its sufferers and their loved ones.

It is rapidly becoming one of the leading diseases among elderly people worldwide. The average cost of treatment and care for an Alzheimer's patient is over US$100,000 worrying many that this will over-stretch preciously thin health budgets if baby-boomers begin to fall ill in the same proportions as previous generations.

On November 20, a research team led by Pei Gang of the Shanghai Institute of Biochemistry and Cell Biology (SIBCB) of the Chinese Academy of Sciences (CAS) published its studies in the premier journal Nature Medicine. It was revealed that the activation of a certain part of a brain cell called the 2-adrenergic receptor may well be one of the culprits.

Over decades of research, scientists have learned that a substance known as amyloid plaque is the primary cause of Alzheimer's.

Amyloid plaque is produced by protein metabolism in certain areas of the brain. In healthy people, amyloid plaque is rapidly metabolized by their immune systems. However, if a person's brain cells produce abnormally high levels of amyloid plaque whilst their immune system lessens its ability to cleanse the plaque, it will begin to accumulate in the brain.

This accumulation twists nerve filaments together, killing substantial numbers of nerve cells. However, little is known about how amyloid plaque formation is regulated.

Drug treatments can only reduce the accumulation of amyloid plaques and lessen the symptoms of Alzheimer's disease; however, there is no cure.

Amyloid plaque formation has been the primary concern of Pei and his colleagues, including Ni Yanxiang of SIBCB, the first author of the paper published in Nature Medicine.

"As early as 2001, we have been focusing our studies on a molecule called presenilin, because it has been reported that more than 100 mutations of this molecule are related to Alzheimer's disease," Ni told China Daily.

Among new discoveries, Ni's focus shifted to other substances whose activities are associated with, but not decided by, presenilin. The 2-adrenergic receptor is one of them.

After activating the 2-adrenergic receptor in mice with Alzheimer's disease for a long time, scientists found that a greater accumulation of amyloid plaques developed in the mice's brains. Consequentially, the mice show accelerated syndromes of Alzheimer's disease.

On the other hand, Ni and his colleagues discovered that using a chemical called 2-adrenergic receptor agonist inhibits the plaque's accumulation.

The repeated studies have verified the link between 2-adrenergic receptor and the accumulation of amyloid plaques.

"The discovery implies an innovative way to prevent amyloid plaque formation and the consequential onset of Alzheimer's disease," Ni said. He said his research team has applied to internationally patent using 2-adrenergic receptor agonist to treat Alzheimer's.

There is a long way to go before the discovery can be used to develop a new drug, but Ni said that stress, nervousness and anxiety activate the 2-adrenergic receptor.

"If we try to lead an easy life, avoiding stress as much as possible, we can largely reduce the risk of developing Alzheimer's disease," he said.

The studies by scientists and doctors worldwide could enhance the research of the Shanghai scientists who traced the relationship between Alzheimer's disease and stress.

Late last year, scientists at the US-based Utah University found that eating more fruits and vegetable can slow the decline of an aging person's memory, which is often the first sign of Alzheimer's.

However, a separate study conducted by researchers at the US-based Accera Pharmaceuticals, in Colorado, says that the benefits of eating vegetables should not make people to become vegetarians.

According to their studies, published in Nutrition and Metabolism journal in late 2005, scientists say that a high intake of fat and low consumption of carbohydrates can reduce the deposit of amyloid plaques.

It is also widely observed that moderate wine drinking slows the onset of Alzheimer's.

Besides food and drink, a more active social life could not only delay the onset of the Alzheimer's, but also reduce its effects on diagnosed patients, according to research by David Bennett at the Chicago-based Rush University.

In a study published in early October in the journal Alzheimer's, US scientists discovered that curcumin, an extract from turmeric, curry and ginger, plays a powerful role in curbing the onset of the Alzheimer's.

The study indicates that immunity cells distilled from Alzheimer's patients which have been treated with curcumin are more effective in metabolizing amyloid plaques.

While scientists are further exploring the molecular mechanisms by which curcumin battles the onset of Alzheimer's, traditional Chinese medicine (TCM) doctors say that using herbal extracts could demonstrate TCM's capability to combat the disease.

For a long time, without knowing the name of the disease let alone the molecular mechanisms that cause Alzheimer's, TCM doctors have been documenting its various symptoms. TCM attributes its causes to the exhaustion of the kidney and consumption of brain marrow.

"The principles of (TCM) treatment are tonifying the kidney and activating blood circulation," said Zhu Zhuangzhuang, a gerontics doctor of Wuhan General Hospital of Guangzhou Military Command Zone.

Based on the disease's symptoms, TCM doctors have given combinations of herbs such as shudi (Radix Rehmanniae Praeparata), fuling (Poria), gouqi (Fructus Lycii) and shanyurou (Fructus Corni).

In recent years, extracts of gingko have been tried as a more experimental method to help treat Alzheimer's disease. The resulting data has been positive.

"As of now, scientists cannot clearly explain all of the mechanisms relating to the onset of Alzheimer's, but one thing is clear: It is a result of a combination of factors including the environment, aging, lifestyle and food intake. TCM has an advantage in comprehensively considering the different factors together," Zhu wrote in her review articles.

(China Daily November 28, 2006)     http://www.china.org.cn/english/health/190456.htm

Study: Anesthesia could hasten Alzheimer's
PHILADELPHIA (UPI) -- Inhaled anesthesia increased the number of brain plaques in animals and might hasten the onset of diseases such as Alzheimer's, a U.S. study found.

More than 100 million people worldwide undergo surgery every year, usually under general anesthesia with an inhaled drug. While the drugs affect short-term cognitive ability, there is growing concern they may have a longer or even permanent impact, as well, University of Pennsylvania researchers said.

"This animal study data suggests that we have to at least consider the possibility that anesthetics accelerate certain neurodegenerative disorders," said Roderic Eckenhoff, vice chair of university's Department of Anesthesia and Critical Care.

"In the field of Alzheimer's research, most effort is focused on delaying, not curing the disease. A delay in the onset of Alzheimer's disease of only three to five years would be considered a success. Therefore, if commonly used drugs, like anesthetics, are accelerating this disorder, even by a few years, then a similar success might follow even small changes in the care of the operative patient."

Stress and Alzheimer's possibly linked

SAN DIEGO (UPI) -- The stress of everyday life may add to the accumulation of neurofibrillary tangles, one of the hallmarks of Alzheimer's disease, suggests a U.S. study.

Researchers at the Salk Institute for Biological Studies in San Diego say that aging is still the greatest risk factor for Alzheimer's disease, a number of studies have pointed to stress as a contributing factor.

"A long-term study of about 800 members of religious orders had found that the people who were most prone to stress were twice as likely to develop Alzheimer's disease, but the nature of the link between the two has been elusive," study leader Paul E. Sawchenko, said in a statement.

The findings, published in the Journal of Neuroscience, suggest that the brain-damaging effects of negative emotions are relayed through the two known corticotropin-releasing factor receptors, CRFR1 and CRFR2, which are part of a central switchboard that mediates the body's responses to stress and stress-related disorders.

  
Acupuncture Today; September, 2000, Vol. 01, Issue 09

Alzheimer's Disease and Acupuncture
Treatment Appears to Improve Mood and Cognitive Functions

By Editorial Staff

Alzheimer's disease is the most common cause of intellectual decline and dementia in the elderly, affecting approximately one out of 10 people over age 65 and nearly half over age 85. The condition affects women more frequently than men, and it is characterized by shrinkage of the frontal or temporal lobes and nerve cell death in several areas of the brain, leading to a loss of key mental functions such as memory, learning and concentration.

Several therapies have been employed to slow down or reverse the effects of Alzheimer's disease, ranging from an increased intake of vitamins and antioxidants to using nicotine patches to a new class of drugs called cholinesterase inhibitors. Patches and large doses of vitamins may have unwanted side-effects, however, and the long-term benefits of cholinesterase inhibitors remain largely unknown.

New research presented at the recent World Alzheimer's Conference in Washington, D.C. have shown promising results with another form of treatment: acupuncture. In two separate studies - one at the Wellesley College Center for Research on Women, the other at the University of Hong Kong1,2 - scientists have found that acupuncture can increase a patient's verbal and motor skills and improve mood and cognitive function.

In the first study, Dr. Nancy Emerson Lombardo and a team of colleagues at Wellesley College in Massachuestts studied 11 patients, 10 with Alzheimer's and one with vascular dementia. Subjects were treated with acupuncture twice a week for three months, with each subject receiving a minimum of 22 treatments. Patients were subjected to a variety of tests before and after being treated, including the Cornell Scale for Depression, the Speilberger State Anxiety Inventory, and the Mini-Mental Status Exam (MMSE) for cognitive function.

The researchers found "statistically significant improvements" in the depression and anxiety scores of patients. For example, the average Spielberger anxiety score at the start of treatment was 49.5; at the end of three months, it had decreased to 40.1. Four subjects experienced "substantial improvement" in mood symptoms after undergoing acupuncture; of those whose moods improved, two also showed improved MMSE scores, and a third improved in tests for fluency and naming ability.

While cognitive function was not measured scientifically (no control group was used), Lombardo said that those delivering treatment seemed to note an improvement in their subjects' thinking skills along with the other improvements, which she believes indicates a close relationship between cognitive ability, anxiety and depression.

"I think people should check it out," said Dr. Lombardo. "Besides anxiety and depression, they are likely to have other issues such as pain that can be helped with acupuncture."

In Dr. Kao's study, eight patients diagnosed with mild to moderate Alzheimer's disease were treated at the University of Hong Kong. Treatment consisted of needling and fine finger turning at eight acupoints: the si shen cong (Estra 7, four points on the scalp), shen men (HT7 on the wrists) and tai xi (KI3 on the feet). Needles were inserted 0.5 inches at an angle into si shen cong; 0.5 inches directly into shen men; and 0.8 inches directly into tai xi.

Needling for each acupoint lasted a total of 30 minutes, comprising the needle testing and its reinsertion after every 10 minutes of therapy. Patients received a seven-day treatment cycle with a three-day break in between for a total of 30 days.

Patients were graded using the TCM Symptoms Checklist for Alzheimer's and the MMSE exam to measure their levels of orientation; memory; attention; and the ability to name an object, follow verbal and written commands, and write a sentence spontaneously.

After being treated, Kao's team reported that patients "significantly improved" on measures of verbal orientation and motor coordination and had higher overall MMSE scores. They also noted that patients "showed a significant overall clinical improvement" on the TCM checklist, leading the researchers to conclude that acupuncture treatment "has shown significant therapeutic effects" in reducing the symptoms of Alzheimer's disease.

Treatments May Provide Hope for Millions of Sufferers

As the average life expectancy has increased over the past few decades, so have the number of people with Alzheimer's disease. Unless a cure or other preventive measure is found, the Alzheimer's Association estimates that by the year 2025, 22 million individuals worldwide will develop Alzheimer's disease.

Admittedly, the research conducted by Kao and Lombardo cannot be considered definitive. Both studies used small patient bases (a total of 19 patients were involved); neither team employed a control group; and some patients didn't respond to treatment as well as others.

Nevertheless, these studies represent an important step forward in the research of both acupuncture and Alzheimer's disease. Because they showed such promising results, the work by Kao and Lombardo could help lay the groundwork for larger, controlled investigations to determine how acupuncture combats Alzheimer's, which could eventually lead to safer, inexpensive forms of care for the more than four million Americans who currently suffer from the disease.

References

Emerson Lombardo N, et al. Acupuncture to treat anxiety and depression in Alzheimer's disease and vascular dementia: a pilot feasibility and effectiveness trial. Presented at the World Alzheimer's Conference, Washington, D.C., July 9-18, 2000.
Kao H, et al. Acupuncture enhancement in clinical symptoms and cognitive-motor abilities of the Alzheimer's disease patients. Presented at the World Alzheimer's Conference, Washington, D.C., July 9-18, 2000.
 

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