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

Novel culture system replicates course of Alzheimer's disease, confirms amyloid hypothesis

3-D system should significantly reduce time and costs of drug development

2014-10-12
(Press-News.org) An innovative laboratory culture system has succeeded, for the first time, in reproducing the full course of events underlying the development of Alzheimer's disease. Using the system they developed, investigators from the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) now provide the first clear evidence supporting the hypothesis that deposition of beta-amyloid plaques in the brain is the first step in a cascade leading to the devastating neurodegenerative disease. They also identify the essential role in that process of an enzyme, inhibition of which could be a therapeutic target.

"Originally put forth in the mid-1980s, the amyloid hypothesis maintained that beta-amyloid deposits in the brain set off all subsequent events – the neurofibrillary tangles that choke the insides of neurons, neuronal cell death, and inflammation leading to a vicious cycle of massive cell death," says Rudolph Tanzi, PhD, director of the MGH Genetics and Aging Research Unit and co-senior author of the report receiving advance online publication in Nature. "One of the biggest questions since then has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons. In this new system that we call 'Alzheimer's-in-a-dish,' we've been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death."

While the mouse models of Alzheimer's disease that express the gene variants causing the inherited early-onset form of the disease do develop amyloid plaques in their brains and memory deficits, the neurofibrillary tangles that cause most of the damage do not appear. Other models succeed in producing tangles but not plaques. Cultured neurons from human patients with Alzheimer's exhibit elevated levels of the toxic form of amyloid found in plaques and the abnormal version of the tau protein that makes up tangles, but not actual plaques and tangles.

Genetics and Aging Research Unit investigator Doo Yeon Kim, PhD, co-senior author of the Nature paper, realized that the liquid two-dimensional systems usually used to grow cultured cells poorly represent the gelatinous three-dimensional environment within the brain. Instead the MGH team used a gel-based, three-dimensional culture system to grow human neural stem cells that carried variants in two genes – the amyloid precursor protein and presenilin 1 – known to underlie early-onset familial Alzheimer's Disease (FAD). Both of those genes were co-discovered in Tanzi's laboratory.

After growing for six weeks, the FAD-variant cells were found to have significant increases in both the typical form of beta-amyloid and the toxic form associated with Alzheimer's. The variant cells also contained the neurofibrillary tangles that choke the inside of nerve cells causing cell death. Blocking steps known to be essential for the formation of amyloid plaques also prevented the formation of the tangles, confirming amyloid's role in initiating the process. The version of tau found in tangles is characterized by the presence of excess phosphate molecules, and when the team investigated possible ways of blocking tau production, they found that inhibiting the action of an enzyme called GSK3-beta – known to phosphorylate tau in human neurons – prevented the formation of tau aggregates and tangles even in the presence of abundant beta-amyloid and amyloid plaques

"This new system – which can be adapted to other neurodegenerative disorders – should revolutionize drug discovery in terms of speed, costs and physiologic relevance to disease," says Tanzi. "Testing drugs in mouse models that typically have brain deposits of either plaques or tangles, but not both, takes more than a year and is very costly. With our three-dimensional model that recapitulates both plaques and tangles, we now can screen hundreds of thousands of drugs in a matter of months without using animals in a system that is considerably more relevant to the events occurring in the brains of Alzheimer's patients."

INFORMATION: Tanzi is the Kennedy Professor of Child Neurology and Mental Retardation, and Kim is an assistant professor of Neurology at Harvard Medical School. Se Hoon Choi, PhD, and Young Hye Kim of the MGH Genetics and Aging Research Unit are co-lead authors of the Nature paper. The study was supported by a grant from the Cure Alzheimer's Fund and by National Institute of Health grants 5P01AG15379 and 5R37MH060009.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $785 million and major research centers in HIV/AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.


ELSE PRESS RELEASES FROM THIS DATE:

Icebergs once drifted to Florida, new climate model suggests

Icebergs once drifted to Florida, new climate model suggests
2014-10-12
AMHERST, Mass. – Using a first-of-its-kind, high-resolution numerical model to describe ocean circulation during the last ice age about 21,000 year ago, oceanographer Alan Condron of the University of Massachusetts Amherst has shown that icebergs and meltwater from the North American ice sheet would have regularly reached South Carolina and even southern Florida. The models are supported by the discovery of iceberg scour marks on the sea floor along the entire continental shelf. Such a view of past meltwater and iceberg movement implies that the mechanisms of abrupt ...

Researchers develop new cells meant to form blood vessels, treat peripheral artery disease

Researchers develop new cells meant to form blood vessels, treat peripheral artery disease
2014-10-12
VIDEO: Researchers have developed a technique to jump-start the body's systems for creating blood vessels, opening the door for potential new treatments for diseases whose impacts include amputation and blindness.... Click here for more information. INDIANAPOLIS -- Researchers have developed a technique to jump-start the body's systems for creating blood vessels, opening the door for potential new treatments for diseases whose impacts include amputation and blindness. The ...

Revving up fluorescence for superfast LEDs

Revving up fluorescence for superfast LEDs
2014-10-12
DURHAM, N.C. -- Duke University researchers have made fluorescent molecules emit photons of light 1,000 times faster than normal -- setting a speed record and making an important step toward realizing superfast light emitting diodes (LEDs) and quantum cryptography. This year's Nobel Prize in physics was awarded for the discovery of how to make blue LEDs, allowing everything from more efficient light bulbs to video screens. While the discovery has had an enormous impact on lighting and displays, the slow speed with which LEDs can be turned on and off has limited their ...

Bioinspired coating for medical devices repels blood and bacteria

2014-10-12
From joint replacements to cardiac implants and dialysis machines, medical devices enhance or save lives on a daily basis. However, any device implanted in the body or in contact with flowing blood faces two critical challenges that can threaten the life of the patient the device is meant to help: blood clotting and bacterial infection. A team of Harvard scientists and engineers may have a solution. They developed a new surface coating for medical devices using materials already approved by the Food and Drug Administration (FDA). The coating repelled blood from more ...

Atomic map reveals clues to how cholesterol is made

Atomic map reveals clues to how cholesterol is made
2014-10-12
In spite of its dangerous reputation, cholesterol is in fact an essential component of human cells. Manufactured by the cells themselves, it serves to stiffen the cell's membrane, helping to shape the cell and protect it. By mapping the structure of a key enzyme involved in cholesterol production, Rockefeller University researchers and a colleague in Italy have gained new insight into this complex molecular process. "This is the first report to pinpoint the location of every atom — in this case nearly 3,000 of them — in one of the membrane-embedded enzymes ...

Solid nanoparticles can deform like a liquid

2014-10-12
CAMBRIDGE, Mass--A surprising phenomenon has been found in metal nanoparticles: They appear, from the outside, to be liquid droplets, wobbling and readily changing shape, while their interiors retain a perfectly stable crystal configuration. The research team behind the finding, led by MIT professor Ju Li, says the work could have important implications for the design of components in nanotechnology, such as metal contacts for molecular electronic circuits. The results, published in the journal Nature Materials, come from a combination of laboratory analysis and computer ...

Australian teams set new records for silicon quantum computing

2014-10-12
Two research teams working in the same laboratories at UNSW Australia have found distinct solutions to a critical challenge that has held back the realisation of super powerful quantum computers. The teams created two types of quantum bits, or "qubits" – the building blocks for quantum computers – that each process quantum data with an accuracy above 99%. The two findings have been published simultaneously today in the journal Nature Nanotechnology. "For quantum computing to become a reality we need to operate the bits with very low error rates," says Scientia ...

Researchers compare efficacy of 'natural' bed bug pesticides

2014-10-12
Concerns over human-insecticide exposure has stimulated the development of alternative bed bug control materials, and many essential oil-based pesticides and detergent insecticides have been developed in recent years. But how well do they work? To find out, researchers from Rutgers University evaluated the efficacy of nine essential oil-based products and two detergents that are labeled and marketed for bed bug control. The results are published in an article in the Journal of Economic Entomology. The non-synthetic bed bug pesticides — which contain ingredients ...

Oral capsule as effective as invasive procedures for delivery of fecal transplant

2014-10-11
A noninvasive method of delivering a promising therapy for persistent Clostridium difficile (C. difficile) infection appears to be as effective as treatment via colonoscopy or through a nasogastric tube. In their JAMA report, receiving early online release to coincide with a presentation at the Infectious Diseases Society of America's ID Week conference, investigators from Massachusetts General Hospital (MGH) report that oral administration of the therapy called fecal microbiota transplant (FMT) in acid-resistant capsules was as successful as more invasive methods in eliminating ...

Treating C. diff infection with oral, frozen encapsulated fecal material

2014-10-11
A preliminary study has shown the potential of treating recurrent Clostridium difficile infection (a bacterium that is one of the most common causes of infection of the colon) with oral administration of frozen encapsulated fecal material from unrelated donors, which resulted in an overall rate of resolution of diarrhea of 90 percent, according to a study published in JAMA. The study is being released early online to coincide with its presentation at IDWeek 2014. Recurrent Clostridium difficile infection (CDI) is a major cause of illness and death, with a recent increase ...

LAST 30 PRESS RELEASES:

Global trust in science remains strong

New global research reveals strong public trust in science

Inflammation may explain stomach problems in psoriasis sufferers

Guidance on animal-borne infections in the Canadian Arctic

Fatty muscles raise the risk of serious heart disease regardless of overall body weight

HKU ecologists uncover significant ecological impact of hybrid grouper release through religious practices

New register opens to crown Champion Trees across the U.S.

A unified approach to health data exchange

New superconductor with hallmark of unconventional superconductivity discovered

Global HIV study finds that cardiovascular risk models underestimate for key populations

New study offers insights into how populations conform or go against the crowd

Development of a high-performance AI device utilizing ion-controlled spin wave interference in magnetic materials

WashU researchers map individual brain dynamics

Technology for oxidizing atmospheric methane won’t help the climate

US Department of Energy announces Early Career Research Program for FY 2025

PECASE winners: 3 UVA engineering professors receive presidential early career awards

‘Turn on the lights’: DAVD display helps navy divers navigate undersea conditions

MSU researcher’s breakthrough model sheds light on solar storms and space weather

Nebraska psychology professor recognized with Presidential Early Career Award

New data shows how ‘rage giving’ boosted immigrant-serving nonprofits during the first Trump Administration

Unique characteristics of a rare liver cancer identified as clinical trial of new treatment begins

From lab to field: CABBI pipeline delivers oil-rich sorghum

Stem cell therapy jumpstarts brain recovery after stroke

Polymer editing can upcycle waste into higher-performance plastics

Research on past hurricanes aims to reduce future risk

UT Health San Antonio, UTSA researchers receive prestigious 2025 Hill Prizes for medicine and technology

Panorama of our nearest galactic neighbor unveils hundreds of millions of stars

A chain reaction: HIV vaccines can lead to antibodies against antibodies

Bacteria in polymers form cables that grow into living gels

Rotavirus protein NSP4 manipulates gastrointestinal disease severity

[Press-News.org] Novel culture system replicates course of Alzheimer's disease, confirms amyloid hypothesis
3-D system should significantly reduce time and costs of drug development