PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Scientists establish link between inflammatory process and progression of Alzheimer's disease

Drugs targeting IL-1 beta production may benefit Alzheimer's patients

2012-12-20
(Press-News.org) WORCESTER, MA — An international team of researchers from the University of Massachusetts Medical School, the University of Bonn and the Center for Advanced European Studies and Research in Germany have shown that a well-known immune and inflammatory process plays an important role in the pathology of Alzheimer's disease. This process, which results in the mature production of the pro-inflammatory cytokine called interleukin-1 beta (IL-1B) and is involved in the body's defense against infection, has also been established as a clinical target for rheumatoid arthritis. The finding, published in Nature, points to the possibility that drugs that disrupt the production of IL-1B, such as those for rheumatoid arthritis, may also prove beneficial for patients with Alzheimer's.

"This finding represents an important new clinical target for patients with Alzheimer's disease," said Douglas T. Golenbock, MD, chief of infectious diseases and immunology and professor of medicine and microbiology & physiological systems. "We've known for years that the plaques associated with Alzheimer's were surrounded by microglia, the resident immune cell of the central nervous system. What we didn't know was what role, if any, inflammation played in the progression of the disease. With this link we have a new path to potentially identifying and attacking this horrible disease."

The most common form of dementia, Alzheimer's is a degenerative neurological disorder that leads to memory loss, impaired cognitive function, and eventually death. By 2050 it is predicted that 1 in 85 people will suffer from Alzheimer's disease. There are no available treatments.

A key physiological component of Alzheimer's disease is the presence of extracellular plaques, primarily composed of beta amyloid peptides, which aggregate in the brain. These plaques are believed to be toxic and the chief cause of nearby neuron death and cortical material loss. The hippocampus, which plays an important role in short-term memory, is one of the first regions of the brain to suffer damage from Alzheimer's.

Golenbock and colleagues had established in previous studies that neurons in cell cultures died after nearby microglia cells, the main form of active immune defense in the brain and spinal cord, were exposed to amyloid beta fibrils, such as those found in Alzheimer's plaques. Typically, microglias are responsible for removing plaques, damaged neurons and infectious agents from the central nervous system. The beta amyloid peptide, however, generates inflammation in the central nervous system by activating microglia to produce neurotoxic compounds, including cytokines. How this process was being activated in patients with Alzheimer's disease, though, was unclear.

Earlier work done in the Golenbock laboratory demonstrated that beta amyloid peptide could induce the production of IL-1B by activating a multi-protein receptor complex in microglial cells known as the NLRP3 inflammasome. Because of its ability to sense the beta amyloid peptide, the NLRP3 inflammasome has been implicated in several chronic inflammatory diseases, including gout and asbestosis. Examining Alzheimer's tissue samples, scientists found that "every one of the cell samples contained increased evidence of activated inflammasomes, strongly suggesting that they were producing IL-1B," said Golenbock.

"Taken together with our earlier studies, this strongly suggested a role for NLRP3 and caspase-1 in producing IL-1B leading to Alzheimer's disease progression," Golenbock said.

To assess the precise impact of NLRP3 and caspase-1 on Alzheimer's disease in an organism, researchers recorded cognitive function and memory in mice models that expressed genes associated with familial Alzheimer's but that were deficient in NLRP3 or caspase-1, and compared them with Alzheimer's mice that had otherwise intact immune systems. When researchers performed memory recall tests of the Alzheimer's in NLRP3- or caspase-1- mutant mice, they found the animals exhibited far better memory recall and appeared protected from memory loss. However, Alzheimer's mice that expressed NLRP3 and caspase-1 at normal levels exhibited symptoms consistent with Alzheimer's disease. Further examination revealed that NLRP3 and caspase-1 deficient mice showed a decrease in beta amyloid plaques and in increased ability of the microglia to remove fibrillar beta amyloid from the brain.

It was also revealed that activated IL-1 levels in the NLRP3 and caspase-1deficient mice were reduced compared to symptom-bearing counterparts. Because of NLRP3 and caspase-1 deficits, these mice produced less IL-1. These deficits appeared to promote formation of a microglia cell phenotype which was more capable of metabolizing and removing Alzheimer's plaques from the central nervous system.

"These findings suggest that a knockout of NLRP3, caspase-1 or mature IL-1B may represent a novel therapeutic intervention for Alzheimer's disease," said Golenbock. "It's possible that drugs that block NLRP3 or IL-1B – including some of which are already in clinical trials or on the market – might provide some benefit," said Golenbock.

"The critical part, though, is how much NLRP3 or IL-1B production can these drugs disrupt," said Golenbock. "I believe that it's not enough to block just 90 percent; it will probably have to be closer to 100 percent."

### About the University of Massachusetts Medical School The University of Massachusetts Medical School has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $250 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.


ELSE PRESS RELEASES FROM THIS DATE:

NYSCF and CUMC scientists develop scientific technique to help prevent inherited disorders in humans

2012-12-20
NEW YORK, NY (December 19, 2012) – A joint team of scientists from The New York Stem Cell Foundation (NYSCF) Laboratory and Columbia University Medical Center (CUMC) has developed a technique that may prevent the inheritance of mitochondrial diseases in children. The study is published online today in Nature. Dieter Egli, PhD, and Daniel Paull, PhD, of the NYSCF Laboratory with Mark Sauer, MD, and Michio Hirano, MD, of CUMC demonstrated how the nucleus of a cell can be successfully transferred between human egg cells. This landmark achievement carries significant implications ...

Asthmatics at increased risk of pulmonary embolism

2012-12-20
People with asthma have an increased risk of pulmonary embolism, according to new research. A new study, published online ahead of print today (20 December 2012) in the European Respiratory Journal, looked at whether people with moderate or severe asthma had an increased risk of developing deep vein thrombosis, or pulmonary embolism. Pulmonary embolism is when the main artery of the lung or the bronchi becomes blocked. It usually results from deep vein thrombosis; a blood clot in the veins, which can break off and move around the body to the lung. Previous research ...

Pics, shoots and leaves: Ecologists turn digital cameras into climate change tools

2012-12-20
As digital cameras become better and cheaper, ecologists are turning these ubiquitous consumer devices into scientific tools to study how forests are responding to climate change. And, they say, digital cameras could be a cost-effective way of visually monitoring the spread of tree diseases. The results – which come from 38,000 photographs – are presented at this week's British Ecological Society's Annual Meeting at the University of Birmingham. Because trees fix carbon dioxide (CO2) from the atmosphere and store carbon as biomass and soil organic matter, forests play ...

Environmental performance affected by ethnicity and religion

2012-12-20
Ethnically or religiously diverse countries underinvest in measures to improve their environmental performance, according to new research by an academic at the University of East Anglia (UEA). Dr Elissaios Papyrakis also found that religious diversity has a more detrimental impact on environmental performance than ethnic differences. These social differences, if they cannot be overcome, may lower collective action and reduce public spending on environmental protection and performance. The study, Environmental Performance in Socially Fragmented Countries, is published ...

Successful solo rock/pop stars twice as likely to die early as those in a band

2012-12-20
[Dying to be famous: retrospective cohort study of rock and pop star mortality and its association with adverse childhood experiences doi 10.1136/bmjopen-2012-002089] Successful solo rock/pop stars are around twice as likely to die early as those in equally famous bands, indicates research published in the online journal BMJ Open. And those who died of drug and alcohol problems were more likely to have had a difficult or abusive childhood than those dying of other causes, the findings showed. The authors included 1489 North American and European rock and pop stars ...

Regular family meals together boost kids' fruit and vegetable intake

2012-12-20
[Family meals can help children reach their 5 A Day: a cross-sectional survey of children's dietary intake from London primary schools Online First doi 10.1136/jech-2012-201604] Regular family meals round a table boosts kids' fruit and vegetable intake, and make it easier for them to reach the recommended five portions a day, indicates research published online in the Journal of Epidemiology and Community Health. The World Health Organization recommends a daily intake of five 80g portions of fruit and vegetables to promote good health and stave off serious disease and ...

Around 2 queries a week to UK poisons service concern...snakebites

2012-12-20
[Snakebite enquiries to the UK National Poisons Information Service: 2004-2010 doi 10.1136/emermed-2012-201587] Snakebite injuries account for around two phone queries every week to the UK National Poisons Information Service, indicates an audit published online in Emergency Medicine Journal. Changes in data recording mean that these figures are probably an underestimate of the true numbers of snakebite injuries in the UK, suggest the authors. They audited telephone enquiries made to the Cardiff, Edinburgh, Birmingham and Newcastle units of the UK National Poisons ...

Gene therapy cocktail shows promise in long-term clinical trial for rare fatal brain disorder

Gene therapy cocktail shows promise in long-term clinical trial for rare fatal brain disorder
2012-12-20
(Embargoed) CHAPEL HILL, N.C. – Results of a clinical trial that began in 2001 show that a gene therapy cocktail conveyed into the brain by a molecular special delivery vehicle may help extend the lives of children with Canavan disease, a rare and fatal neurodegenerative disorder. A report of the trial appears in the Dec. 19, 2012 online edition of the journal Science Translational Medicine. The form of gene therapy was created and developed at the University of North Carolina School of Medicine. The work was spearheaded by R. Jude Samulski, PhD, a study senior author, ...

New study sheds light on dinosaur size

2012-12-20
Dinosaurs were not only the largest animals to roam the Earth - they also had a greater number of larger species compared to all other back-boned animals - scientists suggest in a new paper published in the journal PLOS ONE today. The researchers, from Queen Mary, University of London, compared the size of the femur bone of 329 different dinosaur species from fossil records. The length and weight of the femur bone is a recognised method in palaeontology for estimating a dinosaur's body mass. They found that dinosaurs follow the opposite pattern of body size distribution ...

Stem cell research shows ALS may be treatable

2012-12-20
Boston – Results from eleven independent ALS (Lou Gehrig's Disease) research studies are giving hope to the ALS community – showing for the first time that the disease may be treatable by targeting new mechanisms revealed by neural stem cell-based studies. A decade of research conducted at multiple institutions, shows that when neural stem cells were transplanted into multi-levels of the spinal cord of a mouse model with familial ALS, disease onset and progression slowed, motor and breathing function improved and treated mice survived three to four times longer than untreated ...

LAST 30 PRESS RELEASES:

Researchers find thousands of pediatric firearm deaths linked to more permissive state gun laws

Landmark test for coeliac disease promises to take away the pain of diagnosis

A recipe for success: beefing up the taste of cultured meat with amino acids

Protecting peppers from devastating viral diseases through gene pyramiding

Lizards of Madagascar

Beyond the brain: how BCIs are rewiring medicine and redefining humanity

Fossilized dinosaur gut shows that sauropods barely chewed

School dental treatments stop kids’ tooth decay in its tracks

How high is your dementia risk? It might depend on where you live

Firearm laws and pediatric mortality in the US

Use of the 988 Suicide and Crisis Lifeline at national, regional, and state levels

Location of firearm suicides in the United States

Discovery suggests method to offset antibiotic-caused harm to infant immune systems

SNU researchers develop world's first 3D microphone capable of position estimation with a single sensor

Cryo-EM structures of isovaleryl-CoA dehydrogenase offers new therapeutic strategies for inherited isovaleric acidemia

JMIR Human Factors invites submission on human factors in health care

New book: Machine Learning in Quantum Sciences

Partnership to support Indigenous researchers, ensure that cancer research reflects the needs of Indigenous groups and that it results in better care

Mount Sinai Health System earns several prestigious national honors for environmental excellence

Screen time and emotional problems in kids: A vicious circle?

UC San Diego researchers find evidence of accelerated aging in children with multiple sclerosis

Out of the string theory swampland

Cancer screenings continue years after guidelines change to limit unnecessary tests, study finds

Mood disorders in late-life may be early warning signs for dementia

Could electric fields supercharge immune attack on the deadliest form of brain cancer?

Rutgers Health research identifies new trigger accelerating antibiotic resistance

Who gets targeted in online games? Study maps harassment risk by gender, age, and identity

MBARI research and technology play integral role in new Decade of Action for Cryospheric Sciences

Protected Antarctic oceanic life threatened by ships anchoring, first underwater videos show

Pregnant and bearing the burden of measles outbreaks in Canada

[Press-News.org] Scientists establish link between inflammatory process and progression of Alzheimer's disease
Drugs targeting IL-1 beta production may benefit Alzheimer's patients