Potential For Blood Test To Diagnose Alzheimer's In Earliest Stage

Blood offers promise as a way to detect Alzheimer's disease at its earliest onset, Mayo Clinic researchers say. They envision a test that would detect distinct metabolic signatures in blood plasma that are synonymous with the disease - years before patients begin showing cognitive decline. Their study was recently published online in the journal PLOS ONE.

Researchers analyzed cerebrospinal fluid and plasma samples from 45 people in the Mayo Clinic Study on Aging and Mayo Clinic Alzheimer's Disease Center (15 with no cognitive decline, 15 with mild cognitive impairment and 15 with Alzheimer's disease). They detected significant changes in the cerebrospinal fluid and plasma in those with cognitive decline and Alzheimer's. Most important, changes in plasma accurately reflected changes in the cerebrospinal fluid, validating blood as a reliable source for the biomarker development.

The team uses a relatively new technique called metabolomics, which measures the chemical fingerprints of metabolic pathways in the cell - sugars, lipids, nucleotides, amino acids and fatty acids - to detect the changes. Metabolomics assesses what is happening in the body at a given time and at a fine level of detail, giving scientists insight into the cellular processes that underlie a disease. In this case, the metabolomic profiles showed changes in metabolites related to mitochondrial function and energy metabolism, further confirming that altered mitochondrial energetics is at the root of the disease process.

The researchers hope that identified changes in the metabolic pathways could lead to the panel of biomarkers, which can eventually be used on a larger scale for early diagnosis, monitoring of Alzheimer's progression, and evaluating therapeutic approaches, says co-author Eugenia Trushina, Ph.D., a Mayo Clinic pharmacologist.

"We want to use these biomarkers to diagnose the Alzheimer's disease before symptoms appear - which can be decades before people start exhibiting memory loss," Dr. Trushina says. "The earlier we can detect the disease, the better treatment options we will be able to offer."

Purified Extracts From Green Tea And Red Wine Interrupt Alzheimer's Disease Pathway In Cells

Natural chemicals found in green tea and red wine may disrupt a key step of the Alzheimer's disease pathway, according to new research from the University of Leeds.

In early-stage laboratory experiments, the researchers identified the process which allows harmful clumps of protein to latch on to brain cells, causing them to die. They were able to interrupt this pathway using the purified extracts of EGCG from green tea and resveratrol from red wine.

The findings, published in the Journal of Biological Chemistry, offer potential new targets for developing drugs to treat Alzheimer's disease, which affects some 800,000 people in the UK alone, and for which there is currently no cure.

"This is an important step in increasing our understanding of the cause and progression of Alzheimer's disease," says lead researcher Professor Nigel Hooper of the University's Faculty of Biological Sciences. "It's a misconception that Alzheimer's is a natural part of ageing; it's a disease that we believe can ultimately be cured through finding new opportunities for drug targets like this."

Alzheimer's disease is characterised by a distinct build-up of amyloid protein in the brain, which clumps together to form toxic, sticky balls of varying shapes. These amyloid balls latch on to the surface of nerve cells in the brain by attaching to proteins on the cell surface called prions, causing the nerve cells to malfunction and eventually die.

"We wanted to investigate whether the precise shape of the amyloid balls is essential for them to attach to the prion receptors, like the way a baseball fits snugly into its glove," says co-author Dr Jo Rushworth. "And if so, we wanted to see if we could prevent the amyloid balls binding to prion by altering their shape, as this would stop the cells from dying."

The team formed amyloid balls in a test tube and added them to human and animal brain cells. Professor Hooper said: "When we added the extracts from red wine and green tea, which recent research has shown to re-shape amyloid proteins, the amyloid balls no longer harmed the nerve cells. We saw that this was because their shape was distorted, so they could no longer bind to prion and disrupt cell function.

"We also showed, for the first time, that when amyloid balls stick to prion, it triggers the production of even more amyloid, in a deadly vicious cycle," he added.

Professor Hooper says that the team's next steps are to understand exactly how the amyloid-prion interaction kills off neurons.

"I'm certain that this will increase our understanding of Alzheimer's disease even further, with the potential to reveal yet more drug targets," he said.

Dr Simon Ridley, Head of Research at Alzheimer's Research UK, the UK's leading dementia research charity, which part-funded the study, said: "Understanding the causes of Alzheimer's is vital if we are to find a way of stopping the disease in its tracks. While these early-stage results should not be a signal for people to stock up on green tea and red wine, they could provide an important new lead in the search for new and effective treatments. With half a million people affected by Alzheimer's in the UK, we urgently need treatments that can halt the disease - that means it's crucial to invest in research to take results like these from the lab bench to the clinic."

Gold Nanoparticle Created That Can Transport Powerful Radioactive Particles Directly To Tumors For Treatment

We've all heard that "it's not wise to use a cannon to kill a mosquito." But what if you could focus the cannon's power to concentrate power into a tiny space? In a new study, University of Missouri researchers have demonstrated the ability to harness powerful radioactive particles and direct them toward small cancer tumors while doing negligible damage to healthy organs and tissues. The study is being published this week in PLOS ONE, an international, peer-reviewed and open-access publication.

Typically, when radiation treatment is recommended for cancer patients, doctors are able to choose from several radiopharmaceuticals that use low-energy radiation particles, known as beta particles. For years, scientists have been studying how to use "alpha particles," which are radioactive particles that contain a large amount of energy, in cancer treatments. The challenges to using alpha particles, which are more than 7,000 times heavier than beta particles, include confining the powerful alpha particles in a designated location inside the body while preventing radiation from wandering to healthy organs and tissues.

"If you think of beta particles as slingshots or arrows, alpha particles would be similar to cannon balls," said J. David Robertson, director of research at the MU Research Reactor and professor of chemistry in the College of Arts and Science. "Scientists have had some successes using alpha particles recently, but nothing that can battle different cancers. For example, a current study using radium-223 chloride, which emits alpha particles, has been fast-tracked by the U.S. Food and Drug Administration because it has been shown to be effective in treating bone cancer. However, it only works for bone cancer because the element, radium, is attracted to the bone and stays there. We believe we have found a solution that will allow us to target alpha particles to other cancer sites in the body in an effective manner."

Robertson and researchers from Oak Ridge National Laboratory and the School of Medicine at the University of Tennessee in Knoxville used the element "actinium," which is an element known as an "alpha emitter" because it produces alpha particles. As it decays, actinium creates three additional elements that produce alpha particles. Due to the strength of these particles though, keeping the elements in place at cancer sites was not possible, until Robertson and Mark McLaughlin, MU doctoral student and co-author on the study, designed a gold-plated nanoparticle that serves as a holding cell for the elements, keeping them in place at the cancer site.

Robertson's nanoparticle is a layered device. At the core is the original element, actinium. Robertson's team then added four layers of material and then coated the nanoparticle with gold. This made the nanoparticle strong enough to hold the actinium - and the other alpha emitters that are eventually created - long enough for any alpha particles to destroy nearby cancer cells.

"Holding these alpha emitters in place is a technical challenge that researchers have been trying to overcome for 15 years," Robertson said. "With our nanoparticle design, we are able to keep more than 80 percent of the element inside the nanoparticle 24 hours after it is created."

While alpha particles are extremely powerful, they don't travel very far, so when the nanoparticles get close to cancer cells, the alpha particles move out and destroy the cell much more effectively than current radiation therapy options, Robertson said.

"Previously, basic research had established that scientists can attach antibodies onto gold nanoparticles that help drive the nanoparticles to the tumor sites in the body," Robertson said. "Without that groundbreaking work, we would not have been able to put this puzzle together."

The early-stage results of this research are promising. If additional studies are successful within the next few years, MU officials will request authority from the federal government to begin human drug development (this is commonly referred to as the "investigative new drug" status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for cancer.