Yearly Archives: 2015

Researchers have made a new discovery about Huntington’s disease, showing that the gene that causes the fatal disorder makes an unexpected ”cocktail” of mutant proteins that accumulate in the brain.

The findings are significant because these newly identified mutant proteins kill neurons and build up in regions of the brain that are most affected by the disease. The findings were published in the journal Neuron.

The researchers examined the brains of 12 deceased adult and juvenile patients with Huntington’s disease. They found novel proteins that were abundant in areas of patients’ brains that showed cell death, neuronal loss and other signs of disease, including neuroinflammation.

Along with a protein already implicated in Huntington’s disease, the researchers found four proteins that also contribute to the disease pathology. The disease stems from a genetic mutation in the Huntingtin gene that produces too many copies of a DNA segment known as CAG, which gives rise to a longer Huntingtin protein with toxic effects. However, researchers found that this DNA repeat mutation can undergo a process known as repeat associated non-ATG (RAN) translation, producing four additional damaging repeat proteins that accumulate in the brain. This was a surprise to the researchers because these RAN proteins are made without a signal in the genetic code that was previously thought to be required for protein production. Each of the four RAN proteins contains long repeats of certain single protein building blocks, or amino acids.

Finding these novel RAN proteins in degenerated areas of the brain that were negative for the previously known mutant Huntingtin protein was crucial to linking them to the disease, said Monica Bañez-Coronel, Ph.D., a postdoctoral associate and the first author of the journal article.

Source: University of Florida

Alzheimer’s patients frequently suffer from sleep disorders, mostly even before they become forgetful, and it is known that sleep plays a very important role in memory formation. Researchers have now been able to show for the first time how the pathological changes in the brain act on the information-storing processes during sleep. Using animal models, they were able to decode the exact mechanism and alleviate the impairment with medicinal agents. The study was published in Nature Neuroscience.

The sleep slow waves, also known as slow oscillations, which our brain generates at night, have a particular role in consolidating what we have learned and in shifting memories into long-term storage. These waves are formed via a network of nerve cells in the brain’s cortex, and then spread out into other parts of the brain, such as the hippocampus.

The study used mouse models, which form the same protein deposits, known as β-amyloid plaques, that are visible in human patients. The scientists were able to show that these plaques directly impair the slow wave activity. The scientists also succeeded in decoding this defect at the molecular level: correct spread of the waves requires a precise balance to be maintained between the excitation and inhibition of nerve cells. In the Alzheimer models, this balance was disturbed by the protein deposits, so that inhibition was reduced.

The researchers used this knowledge to treat the defect with medication. One group of sleep-inducing drugs, benzodiazepines, is known to boost inhibitory influences in the brain. If the scientists gave small amounts of this sleep medication to the mice (approximately one-tenth of the standard dose), the sleep slow waves were able to spread out correctly again. In subsequent behavioral experiments, they were able to demonstrate that learning performance had improved as well.

Source: Technical University of Munich

JPND Board Member Dr. John Hardy of the UCL Institute of Neurology was awarded the $3 million Breakthrough Prize in Life Sciences for his pioneering research into the genetic causes of Alzheimer’s disease, other forms of dementia and Parkinson’s disease.

The Breakthrough Prize in Life Sciences honours ‘transformative advances toward understanding living systems and extending human life’. This is the first time that the prize has been awarded to a UK researcher.

Using innovative genetic analysis methods, Professor Hardy has made major contributions to the study of almost all major neurodegenerative diseases. He has published over 850 scientific papers, many of which are focused on neurological disorders and more specifically the genetics of Alzheimer’s disease. His research has underpinned nearly all basic science and treatment research into Alzheimer’s disease over the last 20 years.

“It is a great honour to be awarded the prize for our work dissecting the causes of Alzheimer and Parkinson’s diseases,” Hardy said. ”It is, of course, our hope and aim that this understanding leads to effective treatments…I feel we can beat these diseases.”

Source: UCL

The EU Joint Programme – Neurodegenerative Disease Research (JPND) will shortly begin another action to support working groups on ”Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration”.

The aim of the call is to establish a limited number of transnational, JPND-sponsored expert working groups to address issues of key relevance for the future use of brain imaging techniques in ND research. Each working group can bid up to €50,000 for support of its activities, which are expected to run for a maximum of 6 months.

This will be a 1-step call, anticipated to launch in early January 2016, with a likely submission deadline of March 2016. Further details will be provided on the call launch date in January 2016. However, any new ideas to tackle harmonisation and alignment in brain imaging will be welcome. For example, this may include:

  • Harmonisation of acquisition for current markers (acquisition and harmonisation of procedures, for example, for MR, FDG PET, and EEG signals)
  • Simplification of web access to image analysis environments (improving the secure access to innovative web-based image analysis environments for neurodegenerative diseases)
  • Innovative PET molecular markers (fostering the use of established and experimental PET methods)
  • Innovative ultra-high field (UHF) MR markers

Please Note:

  • Proposals are not limited to these topics, and may cover other topics within harmonisation and alignment of brain imaging methods.
  • All information regarding future JPND Call topics is subject to change.
  • Final call information will be published on the JPND website (www.jpnd.eu).

The diseases covered by JPND are:
– Alzheimer’s disease (AD) and other dementias
– Parkinson’s disease (PD) and PD‐related disorders
– Prion disease
– Motor neurone diseases (MND)
– Huntington’s Disease (HD)
– Spinocerebellar ataxia (SCA)
– Spinal muscular atrophy (SMA)

 

megaphone_announcement.jpgIn 2015, JPND has launched a joint transnational co-funded call in partnership with the European Commission under the ERA-NET Co-fund scheme in three JPND priority areas:

 

Longitudinal Cohort Approaches, Advanced Experimental Models, Risk and Protective Factors.

 

Twenty-one project proposals are recommended for funding by the Peer Review Panel based on scientific excellence and by the Call Steering Committee based on budget availability.

More information here

 

REPORTS AVAILABLE

JPND call 2014:  “ Working Groups to Inform Cohort Studies in Neurodegenerative Disease Research“

 

Increasing the impact of longitudinal population studies for neurodegenerative disease research

The use of population studies offers a significant opportunity for research into factors affecting risk and progression of neurodegenerative disease, an opportunity that is greater than ever given the emergence of new molecular and digital technologies. However, to fully realise this potential there is a need to harmonise approaches and encourage collaboration and data sharing. In response to this, JPND commissioned ten groups of experts through a peer reviewed call for proposals to address methodological challenges preventing current population- and disease-based longitudinal cohorts being fully used for ND research.  A brief description of the valuable reports and recommendations provided by each group is provided below.

Philippe Amouyel, the Chair of JPND comments:

JPND recognises that longitudinal cohort studies are a rich but under-used resource. This is why we designed a rapid-action call to ask leading international experts to put their heads together to help exploit this opportunity and make population studies more accessible to a wider range of researchers. The guidelines that have been provided through this extensive body of work provide an important resource for the scientific community, which will help researchers increase collaborative activity and make productive use of longitudinal cohort studies. 

Reports available here

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The topics for the 5th IMI-2 Call are confirmed and the call is open

The topics for the 5th Call under the Innovative Medicines Initiative 2 are now confirmed, with a heavy emphasis on Alzheimer’s Disease (AD). The following four AD-related topics are included in the call:

– Inflammation and Alzheimer’s disease (AD): modulating microglia function – focussing on TREM2 and CD33

– Understanding the role of amyloid biomarkers in the current and future diagnosis and management of patients across the spectrum of cognitive impairment (from pre-dementia to dementia)

– Evolving models of patient engagement and access for earlier identification of Alzheimer’s disease: phased expansion study

– Apolipoprotein E (ApoE) biology to validated Alzheimer’s disease targets

The call is now open for stage 1 proposals with a deadline of October 13th, 2015. More information is available at the links below:

Links:

Call overview: http://www.imi.europa.eu/content/imi-2-call-5-0

Stage 1 proposals: http://www.imi.europa.eu/content/stage-1-16

The COEN initiative has released its third call for proposals aiming to further catalyse collaborative research to drive a step change in neurodegeneration research.

The Network of Centres of Excellence in Neurodegeneration (COEN) initiative aims to build collaborative research activity in neurodegeneration research across borders, focusing on critical mass and excellence. COEN is aligned with JPND, although it operates as an independent entity.

The third COEN call for research proposals was recently launched by six of the eight COEN members and will provide funds for ‘Pathfinder’ grants for innovative research to underpin new approaches to therapeutic intervention.

As in previous COEN calls, applications will connect centres with a critical mass of resources and expertise to drive a step change in neurodegeneration research. The six agencies are contributing £4.0m to fund awards made under the call involving their national Centres of Excellence.

The remit of the call is broad in scope: projects may include studies to illuminate our understanding of neurodegenerative mechanisms, or create technological advances to support novel diagnostic or therapeutic approaches.

The call will be administered as for the previous COEN pathfinder call, with partners funding research in their own country. The list of awards made under the first two COEN calls is located here.

More information can be found at the COEN website at the link below.  Closing date for submissions is 4pm on the 5th of October 2015 (BST; GMT+1)

Link:      http://www.coen.org/call-for-proposals-2015.html

The Alzheimer’s Association International Conference® (AAIC) is the world’s largest forum for the dementia research community. the 2015 conference takes place in Washington DC between July 18-23rd.

International investigators, clinicians and care providers gather annually to share the latest study results, theories and discoveries to bring the world closer to breakthroughs in dementia science.

As part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

The programme for this year’s meeting is available at the link below.

Research has uncovered further evidence of a system in the brain that persistently maintains memories for long periods of time. And paradoxically, it works in the same way as mechanisms that cause mad cow disease and other degenerative brain diseases.

In four papers published in Neuron and Cell Reports, researchers show how prion-like proteins – similar to the prions behind mad cow disease in cattle and Creutzfeld-Jakob disease in humans – are critical for maintaining long-term memories in mice, and probably in other mammals. The lead authors of the four papers are Luana Fioriti, Joseph Stephan, Luca Colnaghi and Bettina Drisaldi.

When long-term memories are created in the brain, new connections are made between neurons to store the memory. But those physical connections must be maintained for a memory to persist, or else they will disintegrate and the memory will disappear within days.Many researchers have searched for molecules that maintain long-term memory, but their identity has remained elusive.These memory molecules are a normal version of prion proteins, according to new research.

In one of many experiments described in the paper by Luana Fioriti, the researchers challenged mice to repeatedly navigate a maze, allowing the animals to create a long-term memory. But when the researchers knocked out the animal’s CPEB3 gene two weeks after the memory was made, the memory disappeared.

The researchers then discovered how CPEB3 works inside the neurons to maintain long-term memories. ”Like disease-causing prions, functional prions come in two varieties, a soluble form and a form that creates aggregates,” said. Kandel. ”When we learn something and form long-term memories, new synaptic connections are made, the soluble prions in those synapses are converted into aggregated prions. The aggregated prions turn on protein synthesis necessary to maintain the memory.”

As long as these aggregates are present, Kandel says, long-term memories persist. Prion aggregates renew themselves by continually recruiting newly made soluble prions into the aggregates. ”This ongoing maintenance is crucial,” said Dr. Kandel. ”It’s how you remember, for example, your first love for the rest of your life.”

A similar protein exists in humans, suggesting that the same mechanism is at work in the human brain, but more research is needed. ”It’s possible that it has the same role in memory, but until this has been examined, we won’t know,” said Dr. Kandel.  ”There are probably other regulatory components involved,” he added. ”Long-term memory is a complicated process, so I doubt this is the only important factor.

Source:  Medical News Net