A molecular scissor related to Alzheimer’s Disease

An international research team led by the Spanish National Research Council (CSIC) and researchers from Kiel University revealed the atomic-level structure of the human peptidase enzyme meprin ß (beta). The enzyme is related to inflammation, cancer and Alzheimer’s Disease and is involved in cellular proliferation and differentiation. The knowledge of the enzyme structure will allow for the development of a new medication type different from those known up to now. The study was published in the current issue of the journal “Proceedings of the National Academy of Sciences”.

“Now that we know how meprin ß looks, how it works and how it relates to diseases, we can search for substances that stop its enzyme activities when they become harmful”, explains Xavier Gomis-Rüth, researcher at the Molecular Biology Institute of Barcelona, who led the project. Meprin ß is an enzyme that is anchored in the outer wall of cells. Its normal function in the human metabolism is to cut off certain proteins, e.g. growth factors, that are also anchored in the cell wall. In this way meprin ß releases protein fragments into the environment surrounding the cells – a natural and normal process, as long as it occurs at a certain intensity. However, under specific circumstances, meprin ß may function abnormally, and, for example, releases too many protein fragments. The protein pieces than overdo their natural task in the cell surroundings, causing disorder in the human body. Such disorder typically occurs when inflammation, cancer or Alzheimer’s Disease get started.

New research proves the validity of one of the most promising approaches for combating Alzheimer’s disease (AD) with medicines that treat not just some of the symptoms, but actually stop or prevent the disease itself, scientists are reporting. The study, in the journal ACS Medicinal Chemistry Letters, also identifies a potential new oral drug that the scientists say could lead the way.

Wenhui Hu and colleagues point out that existing drugs for AD provide only “minimal” relief of memory loss and other symptoms, creating an urgent need for new medicines that actually combat the underlying destruction of brain cells. Research suggests that inflammation of nerve cells in the brain is a key part of that process. One medicine, Minozac, is in clinical trials. But Hu says Minozac still has more space to improve its efficacy. So the scientists sifted through compounds with a molecular architecture similar to Minozac in an effort to find more active substances.

The report describes success in doing so. They discovered one compound that appeared especially effective in relieving nerve inflammation and in improving learning and memory in lab mice widely used in AD research. “In general, this study not only proves that countering neuroinflammation is indeed a potential therapeutic strategy for Alzheimer’s disease, but also provides a good lead compound with efficacy comparable to donepezil [an existing AD medicine] for further oral anti-AD drug discovery and development,” the report states.

Home-Based Assessment Tool for Dementia Screening

Georgia Tech researchers have created a tool that allows adults to screen themselves for early signs of dementia. The home-based computer software is patterned after the paper-and-pencil Clock Drawing Test, one of health care’s most commonly used screening exams for cognitive impairment.

“Technology allows us to check our weight, blood-sugar levels and blood pressure, but not our own cognitive abilities,” said project leader Ellen Yi-Luen Do. “Our ClockMe System helps older adults identify early signs of impairment, while allowing clinicians to quickly analyze the test results and gain valuable insight into the patient’s thought processes.”

Georgia Tech’s ClockMe system eliminates the paper trail and computerizes the test into two main components: the ClockReader Application and the ClockAnalyzer Application. Click here to see a video demo.

New research in The FASEB Journal suggests that serum from animals such as camels, llamas, and alpacas could enhance brain imaging and help drugs pass through the blood-brain barrier

President Obama’s national plan to fight Alzheimer’s disease just got a lift thanks to a team of international researchers whose recent discovery may lead to enhanced imaging of and improved drug delivery to the brain. A research report appearing in The FASEB Journal, describes an entirely new class of antibody discovered in camelids (camels, dromedaries, llamas, and alpacas) that is able to cross the blood-brain barrier, diffuse into brain tissue, and reach specific targets. Having such antibodies, which are naturally available, may be part of a “game changer” in the outcomes for people with brain diseases that are poorly diagnosed and treated, at best, using today’s tools.

"This basic biological investigation opens new pathways toward innovative therapeutic solutions for intractable diseases such as Alzheimer’s disease or brain tumors," said Pierre Lafaye, Ph.D., a researcher involved in the work from the Institut Pasteur, PF: Production de Protéines Recombinantes et d’Anticorps –Proteopole in Paris, France. "The importance of this study is the hope that this novel approach may be a useful tool in crossing the blood brain barrier for diagnostic and therapeutic purposes," added Babbette Weksler, MD, Professor of Medicine, Weill Cornell Medical College, New York, NY, another author of the study and editorial board member of The FASEB Journal.

New study suggests memory impairment tied to object perception

A new study from Georgia Tech and the University of Toronto suggests that memory impairments for people diagnosed with early stage Alzheimer’s disease may be due, in part, to problems in determining the differences between similar objects. The findings also support growing research indicating that a part of the brain once believed to support memory exclusively – the medial temporal lobe - also plays a role in object perception. The results are published in the October edition of Hippocampus.

Mild cognitive impairment (MCI) is a disorder commonly thought to be a precursor to Alzheimer’s disease. The study’s investigators, partnering with the Emory Alzheimer’s Disease Research Center, tested MCI patients on their ability to determine whether two rotated, side-by-side pictures were different or identical.

Male DNA in women’s brains could protect against Alzheimer’s

Researchers found that up to two thirds of women carry male DNA in their brain, which was most likely passed on to them while pregnant with sons.

The exact medical consequences of the transfer from foetus to mother remains unclear but a study showed it was less common in women who suffered from Alzheimer’s, suggesting that it could offer protection against the condition.

Previous studies insicate that similar processes of DNA transfer could raise the risk of some cancers, such as breast cancer, and lower the risk of others including cancer of the colon.

The new study of brain tissue taken from 59 women who died aged 32 to 101 found male DNA in 63 per cent of specimens.

The findings, published in the Public Library of Science ONE journal, also showed that the male DNA was less common in the parts of the brain most severely damaged by Alzheimer’s.

But the researchers, from the Fred Hutchinson Cancer Research Centre in Seattle, emphsaised that the small scale of the study and the lack of data on the women’s pregnancy history meant the evidence was not conclusive.

Dr William Chan, who led the project, said: “Currently, the biological significance of harbouring male DNA and male cells in the human brain requires further investigation.”

Fly neurons could reveal the root of Alzheimer’s disease, says a TAU researcher

Ya’ara Saad, a PhD candidate in the lab of Prof. Amir Ayali at TAU’s Department of Zoology and the Sagol School of Neurosciences. is exploring how neural networks develop one neuron at a time. In the lab, the researchers break the fly’s nervous system down into single cells, separate these cells, then place them at a distance from each other in a Petri dish. After a few days, the neurons begin to grow towards one another and establish connections, and then migrate to form clusters of cells. Finally, they re-organize themselves to form a sophisticated network, says Saad. Because these experiments uniquely allow researchers to concentrate on individual neurons, they can perform specific measurements of proteins, note electrical activity, watch synapses develop, and see how physical changes take shape.

Saad and her fellow researchers are using this technique to observe how neurodegenerative diseases take over the neurons and to potentially test various medicinal interventions. In their experiments, one group of flies is genetically modified so that it expresses a peptide called Amyloid Beta, found in protein-based plaques of human Alzheimer’s disease patients. The results of these studies are then compared to those of a non-modified control group. Both strains of flies are provided by Prof. Daniel Segal of TAU’s Department of Molecular Microbiology and Biotechnology.

Previous studies performed on flies expressing Amyloid Beta showed that they demonstrate Alzheimer’s-like symptoms such as motor problems, impaired learning capabilities, and shorter lifespans. While this peptide has been researched for quite some time, scientists still do not know how it functions. Saad says her work may help unlock the mystery of this function. “Now I can really get into the molecular operation of Amyloid Beta inside the cell. I can watch the dysfunction in the synapses, monitor the proteins involved, and record electrical activity in a much more accessible way,” she says.