Researchers at NYU School of Medicine have found that elevated cerebrospinal fluid levels of phosphorylated tau231 (P-tau231), a damaged tau protein found in patients with Alzheimer’s disease, may be an early diagnostic biomarker for Alzheimer’s disease in healthy adults. 

The study, published this month online by Neurobiology of Aging, shows that high levels of P-tau231 predict future memory decline and loss of brain gray matter in the medial temporal lobe—a key memory center. Prior studies found the medial temporal lobe to be the most vulnerable brain region in the early stages of Alzheimer’s disease, accumulating damaged tau proteins in the form of neurofibrillary tangles. Tangles are one of the signature indicators of Alzheimer’s disease, in addition to beta amyloid plaques.  

“Our research results show for the first time that elevated levels of P-tau 231 in normal individuals can predict memory decline and accompanying brain atrophy,” said lead author Lidia Glodzik MD, PhD, assistant research professor, Department of Psychiatry at the Center for Brain Health and Center of Excellence on Brain Aging at NYU School of Medicine. “Our findings suggest that P-tau231 has the potential to be an important diagnostic tool in the pre-symptomatic stages of Alzheimer’s disease.”  

Researchers evaluated 57 cognitively healthy older adults and studied the relationships between baseline cerebrospinal fluid biomarkers, longitudinal memory performance and longitudinal measures of the medial temporal lobe gray matter using magnetic resonance imaging, or MRI. Two years later, researchers found that 20 out of 57 healthy adults showed decreased memory performance. The group with worsened memory had higher baseline levels of P-tau231 and more atrophy in the medial temporal lobe. The higher P-tau231 levels were associated with reductions in medial temporal lobe gray matter. Authors concluded that elevated P-tau231 predicts both memory decline and medial temporal lobe atrophy. 

“Indentifying people at risk for Alzheimer’s disease is the necessary first step in developing preventive therapies,” said co-author Mony de Leon, EdD, professor, Department of Psychiatry, and director of the Center for Brain Health at the Center of Excellence on Brain Aging at NYU School of Medicine and research scientist at the Nathan S. Kline Institute for Psychiatric Research. “This study shows that Alzheimer’s disease pathology may be recognized in the normal stages of cognition. This observation may be of value in future studies investigating mechanisms that cause or accelerate dementia.”  

This study was done in collaboration with the Nathan S. Kline Institute for Psychiatric Research (NY), Applied NeuroSolutions, Inc. (IL), QiLu Hospital of Shandong University (China), The Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital (Sweden) and the Institute for Basic Research (NY).  

Funding for this study was provided by the National Institutes of Health (NIH) in Bethesda, Maryland.

The USF-led study in mice indicates long-term exposure to electromagnetic waves emitted by cell phones may even boost normal memory

Tampa, FL (Jan. 6, 2010) – The millions of people who spend hours every day on a cell phone, may have a new excuse for yakking. A surprising new study in mice provides the first evidence that long-term exposure to electromagnetic waves associated with cell phone use may actually protect against, and even reverse, Alzheimer’s disease. The study, led by University of South Florida researchers at the Florida Alzheimer’s Disease Research Center (ADRC), was published today in the Journal of Alzheimer’s Disease.

“It surprised us to find that cell phone exposure, begun in early adulthood, protects the memory of mice otherwise destined to develop Alzheimer’s symptoms,” said lead author Gary Arendash, PhD, Research Professor at the Florida ADRC. “It was even more astonishing that the electromagnetic waves generated by cell phones actually reversed memory impairment in old Alzheimer’s mice.”

Can long-term exposure to cell phone signals help treat or prevent dementia and benefit memory? A new USF study concludes it may.

The researchers showed that exposing old Alzheimer’s mice to electromagnetic waves generated by cell phones erased brain deposits of the harmful protein beta-amyloid, in addition to preventing the protein’s build-up in younger Alzheimer’s mice. The sticky brain plaques formed by the abnormal accumulation of beta amyloid are a hallmark of Alzheimer’s disease. Most treatments against Alzheimer’s try to target beta-amyloid.

The highly-controlled study allowed researchers to isolate the effects of cell phone exposure on memory from other lifestyle factors such as diet and exercise. It involved 96 mice, most of which were genetically altered to develop beta-amyloid plaques and memory problems mimicking Alzheimer’s disease as they aged. Some mice were non-demented, without any genetic predisposition for Alzheimer’s, so researchers could test the effects of electromagnetic waves on normal memory as well.

Both the Alzheimer’s and normal mice were exposed to the electromagnetic field generated by standard cell phone use for two 1-hour periods each day for seven to nine months. The mice didn’t wear tiny headsets or have scientists holding cell phones up to their ears; instead, their cages were arranged around a centrally-located antenna generating the cell phone signal. Each animal was housed the same distance from the antenna and exposed to electromagnetic waves typically emitted by a cell phone pressed up against a human head.

The mice were exposed to cell phone signals from a centrally located antenna.

If cell phone exposure was started when the genetically-programmed mice were young adults -- before signs of memory impairment were apparent -- their cognitive ability was protected. In fact, the Alzheimer’s mice performed as well on tests measuring memory and thinking skills as aged mice without dementia. If older Alzheimer’s mice already exhibiting memory problems were exposed to the electromagnetic waves, their memory impairment disappeared. Months of cell phone exposure even boosted the memories of normal mice to above-normal levels. The memory benefits of cell phone exposure took months to show up, suggesting that a similar effect in humans would take years if cell phone-level electromagnetic exposure was provided.

Based on their promising and unexpected findings in mice, the researchers concluded that electromagnetic field exposure could be an effective, non-invasive and drug-free way to prevent and treat Alzheimer’s disease in humans. They are currently evaluating whether different sets of electromagnetic frequencies and strengths will produce more rapid and even greater cognitive benefits than those found in their current study.

“If we can determine the best set of electromagnetic parameters to effectively prevent beta-amyloid aggregation and remove pre-existing beta amyloid deposits from the brain, this technology could be quickly translated to human benefit against AD” said USF’s Chuanhai Cao, PhD, the other major study author. “Since production and aggregation of β-amyloid occurs in traumatic brain injury, particularly in soldiers during war, the therapeutic impact of our findings may extend beyond Alzheimer’s disease.”

The memory test used to evaluate the effects of cell phone exposure in mice was closely designed from a sensitive test used to determine if Alzheimer’s disease, or its very early signs (mild cognitive impairment), are present in humans. “Since we selected electromagnetic parameters that were identical to human cell phone use and tested mice in a task closely analogous to a human memory test, we believe our findings could have considerable relevance to humans,” Arendash said.

The memory and thinking skills of both Alzheimer's mice and normal mice were tested in a specially-designed water maze with visual cues, before and after long-term exposure to cell phone EMF.

The researchers found a slight increase in brain temperature during the two one-hour periods when mice were exposed to electromagnetic waves each day. This increase in brain temperature was seen only in the Alzheimer’s mice, and only after months of exposure. The researchers suggest the increase in brain temperature helped the Alzheimer’s brain to remove newly-formed beta-amyloid by causing brain cells to release it.

The researchers were particularly surprised to discover that months of cell phone exposure actually boosted the memory of non-demented (normal mice) to above-normal levels. They suspect that the main reason for this improvement involves the ability of electromagenetic exposure to increase brain activity, promoting greater blood flow and increased energy metabolism in the brain. “Our study provides evidence that long-term cell phone use is not harmful to brain,” Dr. Cao said. “To the contrary, the electromagnetic waves emitted by cell phones could actually improve normal memory and be an effective therapy against memory impairment”

“It will take some time to determine the exact mechanisms involved in these beneficial memory effects,” Arendash said. “One thing is clear, however - the cognitive benefits of long-term electromagenetic exposure are real, because we saw them in both protection- and treatment-based experiments involving Alzheimer’s mice, as well as in normal mice.”

USF research professor and neuroscientist Gary Arendash, PD, is lead author of the study. "We did not start out the study thinking we'd see these beneficial effects," he said.

Previous human studies of electromagnetic waves from cell phones involved only brief exposures given to normal humans. While some studies reported small improvements in attention or memory (not enough to impact daily life), others reported no memory effects from short-term exposure. The new study by Arendash, Cao, and their colleagues is the first to investigate the effects of long-term electromagnetic exposure over many months on memory function in either humans or animals. The findings indicate that “long-term” exposure to cell phone level electromagnetic waves is needed to observe enhanced memory in normal or memory-impaired mice.

The USF researchers began investigating the effects of cell phone use on Alzheimer’s disease several years ago, after several observational studies in humans linked a possible increased risk of Alzheimer’s with “low-frequency” electromagnetic exposure -- like the energy waves generated by power and telephone lines. However, cell phones emit “high-frequency” electromagnetic waves, which are very different because they can have beneficial effects on brain cell function, such as increasing brain cell activity, Arendash said.

There has been recent controversy about whether electromagnetic waves from cell phones cause brain cancer. Some researchers argue that the risk of glioma (40 percent of all brain tumors) doubles after 10 or more years of cell phone use. However, others argue that since the overall lifetime risk of developing a brain tumor of any type is less than 1 percent, any doubling of this risk would still be very low. Groups such as the World Health Organization, the American Cancer Society, and the National Institutes of Health, have all concluded that scientific evidence to date does not support any adverse health effects associated with the use of cell phones. Consistent with the view of these organizations, th researchers found no autopsy evidence of abnormal growth in brains of the Alzheimer’s mice following many months of exposure to cell phone-level electromagnetic waves. They also found all major peripheral organs, such as the liver and lungs, to be normal.

The research was conducted by an interdisciplinary group of neuroscientists, electrical engineers, and neurologists from universities in Japan and China as well as from the Florida ADRC at the University of South Florida. The studies were supported by funds from the Florida ADRC, a statewide project sponsored by the National Institute on Aging.

Electromagnetic Field Treatment Protects Against and Reverses Cognitive Impairment in Alzheimer’s Disease Mice. Gary W. Arendash, Juan Sanchez-Ramos, Takashi Mori, Malgorzata Mamcarz, Xiaoyang Lin, Melissa Runfeldt, Li Want, Guixin Zhang, Vasyl Sava, Juan Tan and Chuanhai Cao. Journal of Alzheimer’s Disease, Volume 19:1 (January 2010).

- About USF Health –
USF Health (www.health.usf.edu) is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, the University of South Florida is one of the nation’s top 63 public research universities and one of only 25 public research universities nationwide with very high research activity that is designated as community-engaged by the Carnegie Foundation for the Advancement of Teaching.

- About the Journal of Alzheimer’s Disease -
The Journal of Alzheimer's Disease (http://www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease and clinical trial outcomes. The Journal of Alzheimer's Disease has an Impact Factor of 5.101 according to Thomson Reuters' 2008 Journal Citation Reports. The Journal is published by IOS Press (http://www.iospress.nl).

The study involved a group of 3,020 people aged 65 and older who were enrolled in the Cardiovascular Health Study.    In the study, researchers at Washington University School of Medicine followed the participants for an average of five years to see whether they developed dementia and an average of eight years to see whether they developed cancer.

At the start of the study, 164 people (5.4 percent) already had Alzheimer's disease and 522 people (17.3 percent) already had a cancer diagnosis. During the study, 478 people developed dementia and 376 people developed invasive cancer.     The findings showed that for people who had Alzheimer's disease at the start of the study, the risk of future cancer hospitalization was reduced by 69 percent compared to those who did not have Alzheimer's disease when the study started. For Caucasian people who had cancer when the study started, their risk of developing Alzheimer's disease was reduced by 43 percent compared to people who did not have cancer at the start of the study, although that finding was not evident in minority groups.

The researchers came to the conclusion that people who have Alzheimer's disease may be less likely to develop cancer, and people who have cancer may be less likely to develop Alzheimer's disease. 

"Discovering the links between these two conditions may help us better understand both diseases and open up avenues for possible treatments," said study author Catherine M. Roe, PhD, of Washington University School of Medicine and a member of the American Academy of Neurology (AAN).

The study findings were published in the December issue of Neurology, the medical journal of the AAN.

NEW YORK, Dec. 3 /PRNewswire/ -- Alzheimer's disease (AD) is one of the most heartbreaking diagnoses a person can receive. This irreversible, progressive brain disease slowly destroys memory and thinking skills and eventually even the ability to carry out the simplest tasks. The most common cause of dementia among older people, AD affects as many as 2.4 million to 4.5 million Americans, according to the National Institute on Aging.

Jin Ryoun Kim, assistant professor of chemical and biological engineering at Polytechnic Institute of New York University, has been leading a team of researchers including Paramjit Arora, associate professor in NYU's Department of Chemistry; Mary Cowman, professor in NYU-Poly's Department of Chemical and Biological Science, and Jorge Ghiso, NYU School of Medicine associate professor, to make this debilitating disease a thing of the past.

Kim is interested in developing a biochemical probe that would quickly and quantitatively reveal toxic proteins associated with Alzheimer's. Developing an early, reliable diagnostic tool will enable researchers to develop drug-like compounds to prevent the disease.

What triggers Alzheimer's, Kim explains, is protein aggregation, in which a protein molecule sticks to neighboring identical molecules, ending up as a toxic form that interferes with normal brain functioning. While all humans have these protein molecules, young people's bodies are able to prevent accumulation of toxic forms of the protein. But as people age, they become more vulnerable to their effects.

Toxic molecules generated during the aggregation process have been directly linked to the onset of Alzheimer's. Unfortunately, the toxic molecule is difficult to detect: It's very unstable, and can change shape, structure or biological effect easily and rapidly.

"One of the biggest problems in AD research is the instability of these toxic protein forms," Kim says. "It's very likely that any existing method of finding them might be misleading; that is, it's like going after a moving target. Detection must be very rapid, specific and quantitative, but there's no such method yet."

That's where his research comes in. "We're trying to develop a biochemical compound -- a specific, rapid and quantitative probe -- that can detect the toxic protein molecule and report its presence quantitatively right away," he says. If such a probe can be developed, it could be used to identify drug-like compounds that can prevent the formation of toxic protein forms, and thus prevent the disease itself. The research is being conducted under a two-year $80,000 New Investigator Research Grant from the Alzheimer's Association (www.alz.org). Kim has filed for a provisional patent, based on preliminary data, for a biochemical probe that would quickly and quantitatively reveal toxic proteins associated with Alzheimer's.

"The goal of our research is a world without Alzheimer's disease," says Kim. "If there's no Alzheimer's in the world, maybe I'd have nothing to do, but it's something I wish. Hopefully, using our probe, maybe a solution is just a few years away."

About Polytechnic Institute of New York University

Polytechnic Institute of New York University (formerly Polytechnic University), an affiliate of New York University, is New York's most comprehensive school of engineering, applied sciences, technology and research, and is rooted in Polytechnic's 155-year tradition of invention, innovation and entrepreneurship -- i-squared-e.

The institution, founded in 1854, is one of the nation's oldest private engineering schools. In addition to its main campus at MetroTech Center in downtown Brooklyn, it offers programs at sites throughout the region and around the globe. NYU-Poly has centers in Long Island, Manhattan and Westchester County; globally, it has programs in Israel, China and will be an integral part of NYU's campus in Abu Dhabi opening in autumn 2010.

For more information, visit www.poly.edu.

SOURCE Polytechnic Institute of New York University

JACKSONVILLE, Fla. — In a surprising reversal of long-standing scientific belief, researchers at the Mayo Clinic campus in Florida have discovered that inflammation in the brain is not the trigger that leads to buildup of amyloid deposits and development of Alzheimer's disease.

In fact, inflammation helps clear the brain of these noxious amyloid plaques early in the disease development, as seen from studies in mice that are predisposed to the disorder, say the researchers in the online issue of the FASEB Journal.

"This is the opposite of what most people who study Alzheimer's disease, including our research group, believed," says the study's lead investigator Pritam Das, Ph.D., an assistant professor in the Department of Neuroscience. "And it also suggests that we can take advantage of the brain's own immune cells by directing them to remove amyloid plaques from the brain, thus protecting the brain against their harmful effects."

The study tested the widely held belief that inflammation in the brain increases the production and buildup of a toxic protein known as amyloid beta (Aβ). Clumps of this protein in the brain are the hallmark pathological feature of Alzheimer's disease.

"The belief was that when the brain's immune cells, microglia, are activated following the initial buildup of amyloid plaques, the inflammation that ensues stimulates the brain cell's machinery to produce more Aβ, which then leads to more inflammation," Dr. Das says. "This chronic activation of immune cells results in a self-reinforcing feedback loop that promotes more and more Aβ deposition and inflammation, eventually leading to malfunction and death of brain neurons."

Although this notion, which came mostly from studies in laboratory cells, was accepted throughout the scientific community, the Mayo Clinic researchers developed a way to test it in a living organism — and they expected to see the same result.

"We had initiated these studies using our new in vivo model to confirm whether inducing inflammation in the brain would in fact exacerbate the disease," Dr. Das says.

The researchers used a technique known as "Somatic Brain Transgenesis" to increase expression of Interleukin-6 (IL-6), a cytokine that stimulates an inflammatory immune response in the brains of young mice predisposed to developing age-progressive amyloid plaques. This powerful technology allows researchers to express any gene of interest in specific parts of the body by tagging the gene onto Adeno-associated viruses, which are inert. In this way, they can study the function of any protein in the brain, and also test its potential therapeutic use.

They found that IL-6 triggered inflammation throughout the brain, and they expected to see a big buildup of plaque as well as damage to brain neurons. "Instead, to our surprise, we found that the inflammation prevented plaques from forming and cleared whatever plaque that was already there," Dr. Das says.

Given this unexpected result, they performed additional experiments using different strategies. "First, we expressed IL-6 in the brains of newly born mice that are yet to develop any amyloid plaques and, secondly, we expressed IL-6 in the brains of mice with pre-existing plaque pathology," he says. "In both these cases, we got similar results — the presence of IL-6 leads to the clearance of amyloid plaques from the brain."

The researchers then performed experiments to determine how the amyloid plaques were removed from the brain. Their analysis revealed that the inflammation induced by IL-6 in the brain directed the microglia cells to remove the amyloid plaques from the brain. Microglial cells do this by phagocytosis. "They gobble up the plaque, which they 'see' as a foreign invader, and break it apart," Dr. Das says. Researchers also found that activated microglia cells were closely attached to the plaques and expressed proteins that help in removing the amyloid plaques from the brain. Dr. Das hypothesizes that inflammation helps clear plaque early in the development of Alzheimer's disease, but that at some point, continued production of the amyloid clumps in the brain overwhelms the ability of microglial cells to do their job. At that point, inflammation, chronically activated by presence of the amyloid plaque, can produce its own unhealthy effects on brain function.

"Indeed, it may be feasible to transiently and selectively manipulate the microglia cells to alter amyloid plaques in a manner that is both effective and tolerable," he says. "However, given that chronic inflammation over years of insult may be detrimental, any intervention based on activation of the brain's immune system must clearly strike a balance between the neuroprotective and neurotoxic effects," cautions Dr. Das. "We need to study this phenomenon more thoroughly, but if we are right, it could have implications not only for Alzheimer's disease but also other neurodegenerative disorders characterized by protein buildup in the brain, such as Parkinson's disease."

The study was funded by grants from the American Health Assistance Foundation (AHAF), Mayo Clinic and the National Institutes of Health (NIH).

###

About Mayo Clinic

Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of "the needs of the patient come first." More than 3,300 physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has sites in Rochester, Minn., Jacksonville, Fla., and Scottsdale/Phoenix, Ariz. Collectively, the three locations treat more than half a million people each year. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education visit www.mayo.edu. MayoClinic.com is available as a resource for your health stories.

ARLINGTON, Va. and SAN MATEO, Calif. (October 6, 2009) – Online health and wellness resource Wellsphere today announced that it has exceeded 3,000 members of its blogger network, more than doubling its number of high-quality health writers in the past year.

Owned by online health enterprise HealthCentral, San Mateo-based Wellsphere is one of the fastest growing online health properties, with more than 40% audience growth over the past 6 months. The company’s HealthBlogger Network, which promotes bloggers’ work to Wellsphere’s rapidly growing audience, focuses on bringing high-quality blogs to those seeking health information and support online. The network attracts health bloggers –physicians, health professionals, expert patients, caregivers, reporters, and others – with a commitment to increasing visibility to the writers’ work and providing exclusive access to offers, features and tools for their individual blogs. Writers retain control and ownership of their content (more information on the HealthBlogger Network is available at http://www.wellsphere.com/health-blogger).

“We are thrilled that Wellsphere’s HealthBlogger Network continues to be a popular and useful asset to the many writers sharing their health knowledge and experiences online,” said Christopher M. Schroeder, CEO of HealthCentral. “We share the mission of our bloggers – to make quality health information and support accessible to all those seeking it.” Schroeder will discuss HealthCentral’s commitment to connecting and supporting health seekers with CNN anchor Elizabeth Cohen at San Francisco’s Health 2.0 conference tomorrow.

HealthCentral’s patient and expert voices include Wellsphere’s HealthBlogger Network and more than 200 top health experts in 35+ condition areas.

About HealthCentral                                                                                                                                         

HealthCentral (www.HealthCentral.com) empowers people to improve and take control of their health and well-being through more than 35 condition- and wellness-specific interactive health sites, including Wellsphere.com, one of the fastest growing health and wellness technology companies. HealthCentral is venture backed by IAC/InteractiveCorp, Polaris Ventures, Sequoia Capital, The Carlyle Group and Allen & Company.

A Million Tweets to Remember aims to be largest movement ever on Twitter at http://1mtweets.com/

Toronto, ON – September 21, 2009 – A new and unique Twitter movement launched today with the goal of revolutionizing the way social causes connect with online communities. The movement, called “A Million Tweets to Remember,” (1Mtweets) seeks to digitally memorialize one million people who have lived with Alzheimer’s disease (past or present) by having their loved ones tweet about them at http://1mtweets.com/. The campaign coincides with the launch of World Alzheimer’s Day, a global initiative to raise awareness about Alzheimer’s.

The campaign is the brainchild of Jordan Banks, a committed philanthropist whose personal connection to the disease includes four grandparents who have all lived with Alzheimer’s. More than six million people across North America are currently affected by Alzheimer’s disease.

“I have seen four of my grandparents battle Alzheimer’s and, in their honour, I wanted to do something monumental,” says Jordan Banks. ”Over the past ten years I have dedicated a significant amount of time raising money and awareness for Alzheimer’s research and care, but this time around I really wanted to leverage technology in garnering substantial support around the world.”

In a recent blog post, Internet marketing guru Seth Godin commented on the tremendous opportunities that exist for non-profits to tap into online social networks: “Take a look at the top 100 twitter users in terms of followers. Remember, this is a free tool, one that people use to focus attention and galvanize action …. None of them are non-profits. Where are the big charities, the urgent charities, the famous charities that face such timely needs and are in a hurry to make change? …. The marketing world has changed completely. So has the environment for philanthropic giving. So have the attitudes of a new generation of philanthropists. But if you look at the biggest charities in the country, you couldn't tell …”

1MTweets seeks to prove there is a prominent place for worthy causes within social networks, and that – if engaged in the right way – people will actively network and connect to support and promote causes close to their heart.

“Twitter is a powerful platform,” adds Banks. “The transfer and sharing of information and level of engagement on Twitter is incredible, making it a great resource to raise awareness for Alzheimer’s and memorialize those who have lived with the devastating disease.”

All proceeds from 1Mtweets will be allocated to research projects focused on the aging brain and Alzheimer’s disease through the Alzheimer Society of Canada in collaboration with the American Alzheimer’s Association.