If this process malfunctions, it can result in infectious diseases, as well as cancer, Parkinson’s or Alzheimer’s disease. Biochemists at Frankfurt’s Goethe University, working together with scientists from the University of Tromsø in Norway, the Weizmann Institute in Israel and the Tokyo Metropolitan Institute in Japan have just come up with an explanation as to how autophagosomes know exactly which proteins and organelles they should degrade.

“Although autophagy has been known for more than 30 years, it is astonishing that no-one thought of looking for the receptors that make this process so selective” explains Prof. Ivan Dikic from the Institute of Biochemistry II and the Cluster of Excellence ‘Macromolecular Complexes’ in Frankfurt. He had a head start in this field, since over several years, he and his group have researched and now published their work on another self-cleaning process in the cell: the degradation of small proteins in the proteasome, which acts as a kind of molecular shredder.

“We know that the molecules which are destined to be discarded are marked with the small protein ubiquitin and this is recognised by a receptor located at the gateway to the proteasome. It was natural to suggest a similar recognition mechanism for protein degradation by autophagosomes”, says Dikic.

Unlike the proteasome, which is a complex molecular machine, autophagosomes simply consist of a double membrane that floats around in the cytoplasm. Not unlike white blood cells, they can engulf larger proteins or even whole cell organelles. But since they have no enzymes with which they can digest their own cargo, they fuse with lysosomes. When a Yoshinori Ohsumi’s group in Japan reported that they had discovered ubiquitin-like proteins (ATG8) on the outer surface of the autophagosome and gone on to prove that they were specific for autophagy, Dikic and his colleague Dr. Vladimir Kirkin immediately began their search for potential autophagy receptors that might bind to the family of ATG8 proteins.

The team of international scientists report in the current issue of the renowned journal “Molecular Cell”, that by employing methods from cell biology, biochemistry and mouse genetics, they have been able to identify a further protein, in addition to the known p62/SQSTM1 protein, that may act as a receptor. This is the protein NBR1, which has long been associated with cancer. Both proteins have a similar chain-like structure. At one end they bind to the ubiquitin that marks the protein aggregates and organelles that are to be degraded. Next to the ubiquitin-binding site is a domain that binds to the ATG8 proteins found at the autophagosomal membrane. Here, the protein waste can dock onto the autophagosome and can then be wrapped up in the membrane.

Vladimir Kirkin, who is now at Merck Serono in Darmstadt, is continuing these investigations with the long-term aim of developing new drugs. Dikic and his group are now concentrating on mitochondria – which are implicated in oxidative stress in cells – hoping to locate the receptors for autophagy on these important organelles.

The four-year study involved 749 men and women in Italy who were over age 65 and did not have memory problems at the beginning of the study. Researchers measured the amount of energy exerted in the participants’ weekly physical activities, including walking, climbing stairs, and moderate activities, such as house and yard work, gardening, and light carpentry. By the end of the study, 54 people developed Alzheimer’s disease and 27 developed vascular dementia.

The study found the top one-third of participants who exerted the most energy walking were 27 percent less likely to develop vascular dementia than those people in the bottom one-third of the group. Participants who scored in the top one-third for the most energy exerted in moderate activities lowered their risk of vascular dementia by 29 percent and people who scored in the top one-third for total physical activity lowered their risk by 24 percent compared to those in the bottom one-third.

“Our findings show moderate physical activity, such as walking, and all physical activities combined lowered the risk of vascular dementia in the elderly independent of several sociodemographic, genetic and medical factors,” said study author Giovanni Ravaglia, MD, with University Hospital S. Orsola Malpighi, in Bologna, Italy. “It’s important to note that an easy-to-perform moderate activity like walking provided the same cognitive benefits as other, more demanding activities.”

Ravaglia says it’s possible that physical activity may improve cerebral blood flow and lower the risk of cerebrovascular disease, which is a risk factor for vascular dementia, but further research is needed about the mechanisms operating between physical activity and a person’s memory.

Contrary to some reports, the study found that physical activity was not associated with a reduced risk of Alzheimer’s disease, but Ravaglia says more research is needed before concluding that Alzheimer’s disease is not preventable through exercise.

The study was supported by grants from the Italian Ministry of University and Scientific Research.

The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer’s disease, epilepsy, Parkinson disease, and multiple sclerosis.

For more information about the American Academy of Neurology, visit http://www.aan.com.

American Academy of Neurology (AAN)
1080 Montreal Ave.
St. Paul, MN 55116
United States

http://www.neurology.org

Early diagnosis is the gateway to support and treatment. It is essential so that people can be involved in discussions about their present and later care, and to enable them and their families to plan for the future.

Kate Fearnley, Health and Community Director of Alzheimer Scotland said “We know that dementia is often not diagnosed until many months or even years into the illness and sometimes never diagnosed at all. This target is very welcome because it will mean more people with dementia will be identified and get appropriate support and care whether they live in their own home or a care home”

A diagnosis of dementia has great implications for both the person with dementia and their family. It is therefore crucial that a diagnosis of dementia is followed by appropriate post diagnostic support. People need help to adjust to the diagnosis. It important that information, emotional support, rehabilitation services, counselling as well as diagnostic and treatment services are in place.

Dementia is a key health issue facing Scotland over the coming decades as our population ages. Alzheimer Scotland considers a target for early diagnosis as an important driver in prioritisation of dementia to meet the projected increase.

Alzheimer Scotland

Dementia affects between 58,000 and 65,000 people in Scotland in 2007. Alzheimer’s disease is the main form of dementia. The second most common is vascular dementia. As yet there is no cure.

By 2031 there will be 75% more people with dementia in Scotland.

Alzheimer Scotland is Scotland’s foremost voluntary organisation working for people with dementia and their carers. It:

- speaks out for the rights and concerns of people with dementia and their carers;
- operates services on over 60 sites throughout Scotland providing practical services such as day, evening and weekend centres, home care and befriending and carers’ support services;
- provides the 24 hour national freephone Dementia Helpline (0808 808 3000);
- has a research programme.

Alzheimer Scotland

“Every Presidential candidate needs to understand that Alzheimer’s is an important issue for American voters,” said Harry Johns, President and CEO of the Alzheimer’s Association. “This disease steals millions of lives and threatens to overwhelm our healthcare and long term care systems. The American people understand that more must be done to stop this escalating epidemic and they want a President who will act to address the concerns of the millions affected by Alzheimer’s today and those who will face it tomorrow.”

Alzheimer’s Disease Feared More Than Natural Disasters

- The survey revealed that Americans are more afraid of developing Alzheimer’s disease (69 percent) than becoming a victim of a natural disaster, such as a wildfire or hurricane (42 percent).

- Somewhat surprisingly, age does not play a factor here as 18-34 year olds (65 percent) are just as likely as seniors (64 percent) to be concerned about themselves or a family member developing Alzheimer’s.

Alzheimer’s is a Bipartisan Issue

- Today there are as many 5 million Americans living with Alzheimer’s disease and that number is expected to grow to as many as 16 million by 2050. Among voters polled the concern about developing Alzheimer’s cuts across party lines with Republicans (64 percent), Democrats (68 percent), and Independents (66 percent).

An Overwhelming Financial Burden to Families and Health Care System

- Alzheimer’s disease is intrinsically linked to long-term care because many of those with the disease are ultimately placed in long term care facilities when families can no longer provide the round-the-clock care people in the advanced stages of the disease require. Millions of families rely on Medicaid to cover long term care costs due to the fact that caring for someone with Alzheimer’s can quickly deplete family assets.

- This survey found financing the expensive costs of long term care was a key issue on voters’ minds, as almost two thirds (62 percent) polled indicated they would be more likely to vote for a Presidential candidate who sought to increase financial assistance for families taking care of a loved one with Alzheimer’s. Further, almost three out of four (70 percent) said reforming Medicare and Medicaid to provide better care for the growing Alzheimer disease population could be a determining factor in who they would choose as the next president.

Women are more likely to vote for candidate who addresses Alzheimer issues

- Women are more likely to vote for a candidate who supports increasing government funding for Alzheimer’s research (72 percent vs. 63 percent of men); women are more likely to choose a candidate who supports Medicare and Medicaid reforms to help those living with Alzheimer’s receive better care (77 percent vs. 66 percent of men); and they are more likely to vote for candidates who support increased financial assistance for persons with Alzheimer’s to receive long term care (69 percent vs. 59 percent of men.)

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. For more information, visit http://www.alz.org.

The Alzheimer’s Association Survey

The Alzheimer’s Association poll, conducted by Peter D. Hart Research Associates, Inc., was created to measure the impact of how Alzheimer issues would impact voters. The nationwide survey was conducted via telephone with a random sample of 801 adults. The overall sampling error for this survey is +/- 3.5%.

Alzheimer’s Association

They used a genetic mouse model that develops Alzheimer’s-like symptoms in adulthood, and over a 25 week period supplemented the regular, balanced diet of half the animals with 10% sugar water. Afterwards, they compared the metabolism, memory skills (by means of various mazes) and brain composition of the regular and sugar-fed mice.

The sugar-fed mice gained about 17% more weight than controls, had higher cholesterol levels, and developed insulin resistance. These mice also had worse learning and memory retention and their brains contained over twice as many amyloid plaque deposits, an anatomical hallmark of Alzheimer’s.

Although the researchers cannot be certain if the increased mental impairment resulted specifically from the higher sugar intake or higher calories in general, these results to highlight the potential risk of sugary beverages. They note that the human equivalent of the mouse diet would be roughly 5 cans of soda per day, although since mice have a higher metabolism, it may actually take less sugar intake in humans.

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society’s student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society’s purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society’s Web site at http://www.asbmb.org.

American Society for Biochemistry and Molecular Biology (ASBMB)
9650 Rockville Pike
Bethesda, MD 20814-3996
United States

http://www.asbmb.org

A world leader in developing molecular imaging agents, Avid’s technology can target amyloid plaque in the brain for detection and diagnosis of Alzheimer’s disease (AD), which affects approximately 4.5 million Americans.

According to the Alzheimer’s Association, it is estimated that a new case of AD occurs in the U.S. every 72 seconds, and by mid century the rate will greatly increase to one case every 33 seconds. The potential benefits of Avid’s technology to the patient and overall public health are very promising, generating strong demand.

Avid’s first novel compound 18F-AV1/ZK (AV-1), devised for early diagnosis and disease progression monitoring of AD, has completed Phase I clinical trials and is to be used in conjunction with positron emission tomography (PET).

Building on the positive clinical data with AV-1, Avid advanced a series of second generation PET molecular imaging compounds into clinical trials – these compounds provide further improvements in image quality for detecting amyloid plaque in the brains of people with AD. Avid is also testing related compounds in clinical trials for use with single photon emission computed tomography (SPECT).

“By accurately diagnosing AD in its earliest stages, Avid’s products may enable more appropriate treatment plans to be devised for patients, thus reducing the long-term cost of care,” says Frost & Sullivan Research Analyst Samantha Barbosa. “Bayer Schering Pharma has executed a licensing agreement for Avid’s first agent, AV-1 to develop the compound, underscoring the potential clinical value of this technology in the marketplace. Now, Avid is developing a second generation PET molecular imaging compound in IND clinical trials for imaging amyloid plaques.”

Researchers are also studying the utilization of this compound for monitoring the efficacy of drugs that may reverse or prevent the deposition of amyloid plaque in the brain. Avid’s technology has the potential to yield the first commercially available molecular imaging agent with the capabilities to successfully image plaque in AD patients and others with mild cognitive impairment (MCI).

“The possible value to the end users such as radiologists, neurologists, and nuclear medicine physicians is the concept of early detection of AD at a time when treatment may be more beneficial,” notes Barbosa. “Moreover, with early detection comes early diagnosis and treatment that will enable appropriate life planning.”

Response level in the scientific community is highly enthusiastic since the results from the reports released on the clinical trial showed a positive outcome.

Through its innovative contribution to molecular imaging with amyloid imaging compounds for patients with AD, Avid is poised to make a major impact on the medical imaging industry, and stands to significantly improve management of Alzheimer’s disease. Therefore, Frost & Sullivan is pleased to present Avid with the Technology Innovation of the Year award in molecular imaging.

Each year Frost & Sullivan presents this Award to the company that has demonstrated technological superiority within its industry. The Award recognizes the ability of the company to successfully develop and introduce new technology, formulate a well-designed product family, and make significant product performance contributions to the industry.

Frost & Sullivan Best Practices Awards recognize companies in a variety of regional and global markets for demonstrating outstanding achievement and superior performance in areas such as leadership, technological innovation, customer service, and strategic product development. Industry analysts compare market participants and measure performance through in-depth interviews, analysis, and extensive secondary research in order to identify best practices in the industry.

About Avid Radiopharmaceuticals, Inc.

Avid Radiopharmaceuticals, Inc. is a product-focused molecular imaging company developing novel diagnostic imaging agents to enable earlier diagnosis and more effective treatment selection and therapeutic monitoring for patients affected by a range of major medical disorders. The company is a pioneer in the development of molecular imaging agents for Alzheimer’s disease that could lead to earlier diagnosis and better evaluation of drugs designed to prevent or reverse amyloid plaque build-up in the brain. Avid’s technology can be used with imaging technologies such as positron emission tomography (PET) and single photon computed tomography (SPECT). Avid is currently enrolling patients in IND studies of 18F-PET agents for imaging amyloid plaques in Alzheimer’s disease and for imaging the vesicular monoamine transporter (VMAT2) in diseases involving dopaminergic degeneration such as Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Recent research has shown that imaging VMAT2 may also be useful in monitoring the functional viability of beta cells of the pancreas, which could improve efforts to diagnose and monitor progression of diabetes mellitus. The VMAT2 imaging program has grown out of a close collaboration with the University of Michigan as well as the University of Pennsylvania.

http://www.avidrp.com

About Frost & Sullivan

Frost & Sullivan, the Growth Consulting Company, partners with clients to accelerate their growth. The company’s Growth Partnership Services, Growth Consulting and Career Best Practices empower clients to create a growth focused culture that generates, evaluates and implements effective growth strategies. Frost & Sullivan employs over 45 years of experience in partnering with Global 1000 companies, emerging businesses and the investment community from more than 30 offices on six continents.

“To screen without symptoms, unless there is a suspicion of a problem, either by the individual, caregivers, or a physician, may led to negative consequences for the person and for society” says Dr. Boustani, who is a geriatrician.

“There currently is no accurate screening test and we would be faced with an unacceptable number of false positives and false negatives. If we focus on dementia red flags we will be identifying individuals who will have a very high probability of having dementia and be able to focus our resources, including diagnostic testing, on these people,” Dr. Boustani says.

Dementia red flags include medication adherence problems, more than 7 prescribed medications, agitation, multiple falls, and more than 2 hospitalizations or emergency department visits in the past year. Dr. Boustani, who says the healthcare system in the United States misses between 60% and 80% of individuals with dementia, is currently testing ways to help physicians identify dementia red flags in their patients so these missed individuals can be helped.

Someone in the United States develops Alzheimer disease every 72 seconds, according to the Alzheimer’s Association. The average primary care physician sees 2,000 patients per year of whom 300 are aged 65 or older. Of these 24 will develop dementia.

Despite this burden of disease, the benefit-harm ratio of conducting general population-based screening has not yet reached the point where the benefit outweighs the harm, the commentary maintains. Harms include possible stigma, loss of long term care insurance, emotional dislocation for both the individual and family, and resources’ shifting from other health problems.

Dr. Boustani is the author of a 2003 report evaluating the wisdom of routine screening for dementia in primary care settings prepared for the U.S Preventative Services Task Force. The report found that while two-thirds of dementia cases are undetected by the patient’s primary care physician, insufficient data exists to indicate whether or not it is a good idea to administer dementia screening tests to patients who do not have symptoms of memory loss or confusion.

“Pressures to institute screening of unproven benefit could divert much needed resources from the health and social care systems and have an overall negative impact on care for patients with dementia and other illnesses, ultimately delaying the point when dementia screening becomes indicated. The goal should continue to be the best possible care for the most patients, which currently does not include screening for dementia,” the commentary concludes.

‘This shocking report should act as an urgent alarm call to the Government to raise standards in care for people with dementia.

‘These are not new issues, and yet so many older people living with this disease are denied basic dignity. Unless steps are taken to address this, even more people will suffer in silence because the rate of dementia is increasing.

‘Help the Aged has been campaigning for some time on the imporatnce of ensuring dignity for dementia sufferers. We have recently developed a practice guide for individuals working with hospital patients – it is through highlighting good practice and encouraging care homes and hospitals to adopt such approaches that real progress can be made.

‘Health minister Ivan Lewis has announced that a new strategy will be published at a later date – this report today underlines just how much this is needed.’

Notes:

Help the Aged has produced a guide for practitioners caring for people with dementia – please call 020 7239 1891

Help the Aged is the charity fighting to free disadvantaged older people in the UK and overseas from poverty, isolation, neglect and ageism. It campaigns to raise public awareness of the issues affecting older people and to bring about policy change. The Charity delivers a range of services: information and advice, home support and community living, including international development work. These are supported by its paid-for services and fundraising activities – which aim to increase funding in the future to respond to the growing unmet needs of disadvantaged older people. Help the Aged also funds vital research into the health issues and experiences of older people to improve the quality of later life.

Help the Aged urgently needs donations and support to help it in the increasingly challenging fight to free disadvantaged older people from poverty, isolation and neglect.

Progesterone is given with estrogen in hormone replacement therapy. Previous studies have suggested that estrogen offers women some protection against Alzheimer’s disease.

The study’s authors, led by gerontologist Christian Pike of the University of Southern California, asked if the same could be true of progesterone.

In a study highlighted in this week’s issue of the Journal of Neuroscience, Pike’s group reports that progesterone has only limited benefit for mice with Alzheimer’s symptoms when taken alone.

When taken with estrogen, progesterone actually inhibits some of the other hormone’s beneficial effects, the study found.

The problem is not necessarily progesterone itself, Pike said. It could be the constant daily dosage, which fails to replicate the pre-menopausal body’s natural cycles of hormone production.

“This is probably not the best way to be delivering progesterone,” Pike said. “Giving a constant dose of progesterone appears to antagonize a lot of the beneficial effects of estrogen.”

Pike’s group tested progesterone on female mice whose hormone production had been blocked to simulate menopause. The mice, which were genetically predisposed to develop an Alzheimer’s-like disease, showed symptoms within months.

Treatment with estrogen reversed the symptoms, Pike’s group reported. Treatment with progesterone did not.

When the two hormones were given together, progesterone appeared to hinder estrogen’s main beneficial function: preventing the buildup of beta amyloid protein, the key risk factor in Alzheimer’s.

“Estrogen no longer decreases the amount of beta amyloid” when progesterone is present, Pike said.

Progesterone’s effects were not all bad, Pike added. The hormone appeared to inhibit tau hyperphosphorylation, another chemical process implicated in Alzheimer’s.

Progesterone also is known to counteract the increased risk of endometrial cancer from estrogen therapy, which is one reason most women receive both hormones.

Pike said his group’s study should provide guidance for the design of human trials studying hormone therapy and Alzheimer’s. He added that future studies might need to focus both on the dosage and the formulation of progestins — the synthetic versions of progesterone given to humans — as well on the starting age for hormone therapy.

Prior to the study, “we really had no idea what the progestins were doing,” Pike said.

The study was funded by the National Institute on Aging under a large grant to USC’s Roberta Brinton, (Progesterone in Brain Aging and Alzheimer’s Disease), who is leading a university-wide effort to study the effects of hormone therapy on women’s health.

Doctors prescribe hormone therapy to counter some of the harmful consequences of menopause, such as losses in bone density. But other large studies have shown that hormone therapy also increases the risk of breast cancer.

“Our study mirrors to some extent recent clinical observations in women that hormone therapy appears to have both beneficial and deleterious effects,” Pike said.

The other authors of the study were USC graduate students Jenna Carroll and Emily Rosario along with Lilly Chang, research lab specialist in obstetrics and gynecology at USC, Frank Stanczyk, professor of research in obstetrics and gynecology at USC and neurobiologists Salvatore Oddo and Frank LaFerla at the University of California, Irvine.

Dr. Pike’s article, Progesterone and estrogen regulate Alzheimer-like neuropathology in female 3xTg-AD mice, will be appearing in the Nov 28 issue of the Journal of Neuroscience. All articles appearing in The Journal of Neuroscience are embargoed for release to the public until 5 pm Eastern time on the evening before the publication date. This policy applies to members of the media, authors, local institutions’ public information officers and anyone else with access to articles published in the Journal.

This donation, the largest single legacy gift in the Society’s history, will be used to help fund critical Alzheimer research, as well as support other important programs and services. The funds were left to the Alzheimer Society of Canada through the will of an Ottawa resident, who witnessed the devastating effects Alzheimer’s disease had on those in her community and wanted to make a difference.

“We continue to be humbled by the generosity of Canadians, and are particularly grateful for the thoughtfulness behind this very important gift,” says Scott Dudgeon, chief executive officer of the Alzheimer Society of Canada. “Legacy giving is a very satisfying and meaningful way for people to make a difference. It is within reach of everyone, regardless of their economic status, and can be done in a way that doesn’t impact their lifestyle, or that of their family.”

A portion of the funds will be used to support the Alzheimer Society’s Research Program. Celebrating its 20th anniversary in 2007/08, the research program helps support some of the country’s best and brightest minds find answers in revention, treatments, and most importantly, a cure.

“We know that research remains the key to a cure, but there is still much work to be done,” adds Dudgeon. “We need the support of both the Canadian public, as well as the Federal Government, in order to ensure enough dollars are being spent on this very important work.”

With this in mind, the Alzheimer Society of Canada is calling on the federal government to make dementia a national health priority by sponsoring the development of a Canadian Dementia Management Strategy. The strategy would include key issues such as research, prevention, diagnosis, improved treatment, improved care and care for caregivers.

The Society is also calling on Canadians to let their voice be heard by becoming an Alzheimer advocate. By joining together with the Society, people can be part of a powerful tool for change, working to create a future without Alzheimer’s disease.

For more information on Alzheimer’s disease, the Alzheimer Society or our advocacy campaign, please visit http://www.alzheimer.ca.