Author Archives: jpnd

The largest international study ever conducted on Alzheimer’s disease, the I-GAP (International Genomics Alzheimer’s Project) consortium has identified eleven new regions of the genome involved in the onset of the disease.

This research gives an overview of the molecular mechanisms underlying the disease, opening up to a better understanding of the pathophysiology of this disease.

These results, detailed inNature Genetics, could not have been obtained without this unique worldwide collaborative effort.

In addition to the well-established association at the APOE locus, they identified 19 genomic regions significantly associated with late-onset Alzheimer’s disease, 11 of which are new susceptibility loci. Their findings reinforce pathways previously implicated in Alzheimer’s disease pathology, including immune response, inflammation, cell migration and lipid transport pathways. They also suggest new candidate genes and pathways that may be involved in disease risk.

These 11 new confirmed genes can open new avenues in the understanding of the occurrence of Alzheimer’s disease. Thus one of the most significant associations were found in the region HLA-DRB5/DRB1 major histocompatibility complex. This finding is interesting in several ways. First, it confirms the involvement of the immune system in disease. In addition, this same region is also found associated with two other neurodegenerative diseases, multiple sclerosis and Parkinson’s disease.

About I-GAP:http://www.alz.org/news_and_events_21649.asp

University of California Irvine’s trailblazing 90+ Study, aimed at learning more about the “oldest old, will continue for at least another five years, thanks to a $9.5 million renewal grant from the US National Institute on Aging.

The 90+ Study is among the largest studies of the oldest old in the world, with clinical, pathological and genetic research being conducted on more than 1,600 participants. Results obtained thus far have provided researchers across the globe with valuable information about aging."

The UC Irvine study is among the few to look at dementia in people over age 90. With the renewed round of funding over the next five years, 90+ researchers plan to employ PET and MRI scans to address these questions: Why do many of the oldest old have Alzheimer’s or vascular pathology in their brains but not show signs of dementia? Are they in the preclinical stages of disease? Will their cognitive abilities eventually decline?

The researchers also intend to monitor blood pressure and oxygen saturation over 24-hour spans to see if dips in blood pressure, particularly during the night, or periods of fluctuation are associated with cerebral microinfarctions or other diseases of the brain that can cause dementia.

Two 2-step calls are due to launch in early December 2013, with a likely first stage (pre-proposal submission) deadline of February 2014.

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is implementing the priorities identified in itsResearch Strategy through a range of large-scale programmatic initiatives. 

During the first phase of implementation (2012-2014), JPND anticipates the launch of JPND Joint Transnational Calls each year to address high priority areas in neurodegenerative disease research*. 

JPND expects to launch two Joint Transnational Calls later this year aimed at supporting transnational collaborations in the field of neurodegenerative disease research.  The 2-step calls are anticipated to launch in early December 2013, with a likely first stage (pre-proposal submission) deadline of February 2014. 

Further detail will be provided here on the call launch date.  However, the indicative titles of each call are provided below:

“A call for European research projects for Cross-Disease Analysis of Pathways related to Neurodegenerative Diseases”

The aim of the call is to establish a limited number of ambitious, innovative, multi-national and multi-disciplinary collaborative research projects that;

  • combine experimental approaches from fundamental, pre-clinical and/or clinical with computational approaches
  • perform network analyses in different neurodegenerative and other chronic diseases to elucidate the underlying mechanisms common and differing in the investigated diseases
  • will add value to existing research by analysing diseases across traditional clinical boundaries, thereby gaining deeper understanding of the patho-physiological mechanisms of the diseases.

“A call for European research projects for Pilot Studies on Preventive Strategies related to Neurodegenerative Diseases”

The aim of the call is to establish pilot initiatives to develop preventive strategies. Proposals should entail multidisciplinary studies which may focus on new paradigms for multimodal preventive interventions including culture specific aspects, on harmonisation initiatives, or on proof-of-concept, and feasibility studies. Proposals may include research-based evaluation of interventions and validation of outcome measures.

Please Note:   

  • For both calls, JPND will pilot the use of a new online partnering tool. The tool will enable call applicants to showcase their research group’s expertise, search for appropriate partners, pitch call-related ideas and draft their pre- and full-proposals online. The tool will be made available through the JPND website, and will be announced in a JPND News alert in November 2013.Sign up here for JPND website alerts.
  • All information regarding future JPND Call topics is indicative and subject to change.

* The JPND diseases 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)

A chemical substance has been identified which shows signs of being able to halt a range of neurodegenerative diseases in mice.

Researchers at the University of Leicester’s Medical Research Council Toxicology Unit, investigating prion disease in mice, have found a common feature across all types of brain cell death. Looking at the natural defence mechanisms of brain cells, they found that brain cells respond by shutting down protein production when attacked by a virus (in order to halt the virus’s spread).

A range of neurodegenerative diseases involve the formation of faulty or "misfolded" proteins, and these activate similar defence mechanisms. In Parkinson’s Disease it is alpha-synuclein which is the errant protein, in Alzheimer’s Disease it is amyloid and tau, and in the case of Huntingdon’s Disease it is another different protein.

The researchers believe the specific errant protein is irrelevant, because it is how cells deal with misfolded protein which is important. The presence of misfolded proteins causes brain cells to shut down protein production for a long period, eventually resulting in cell death.

The researchers believe they may be able to disrupt this process by the administration of a particular compound, thereby halting neurodegeneration; at least in mice with prion disease so far.

Research teams from Sheffield, UK and Milan, Italy looked at the factors which might explain the differences observed in speed and severity in the progression of motor neuron disease (MND).

Researchers used a scientific technique known as gene expression profiling to identify factors within motor neurones that control vulnerability or resistance to MND in order to shed light on the factors important for the speed of motor neurone injury in human patients.  The research, published in the scientific journal Brain, investigated two mouse models of MND caused by an alteration in the SOD1 gene, a known cause of MND in humans. One of the strains had a rapidly progressing disease course and the other a much slower change in the symptoms of MND.

The study, funded by the Motor Neurone Disease Association, revealed new evidence at the point of onset of the disease, before muscle weakness was observed, showing key differences in major molecular pathways and the way the protective systems of the body responded, between the profiles of the rapid progressing and slow progressing models. In the case of the model with rapidly progressing MND the motor neurones showed reduced functioning of the cellular systems for energy production, disposal of waste proteins and neuroprotection. Motor neurones from the model with more slowly progressing MND showed an increase in protective inflammation and immune responses and increased function of the mechanisms that protect motor neurones from damage.

Neurobiologists from the Friedrich Miescher Institute for Biomedical Research proved that excitability protects motor neurons from degeneration in amyotropic lateral sclerosis, a rare neurodegenerative disease.

By modulating excitability researchers could influence the rate of motor dysfunction and muscle denervation, and slow the progression rate of the disease.

This is important because it points to a possible way to delay the progression of this so far incurable disease.

Their results are published online in Neuron. 

Having depression may increase your risk of developing Parkinson’s disease by up to three times, according to a new study.

Depression is known to raise the risk of a host of diseases including cancer and stroke, but although it is known to be more common among Parkinson’s patients than the general population, it remains unclear whether it is a cause or a symptom.

Researchers from Taipei Veterans General Hospital in Taiwan examined the medical records of 4,634 people who suffered from clinically diagnosed depression, and 18,544 who did not, over a ten-year period.
They found that 66 people with depression, or 1.42 per cent, went on to be diagnosed with Parkinson’s during the next decade compared with 97 of those without depression, or 0.52 per cent.

After other factors such as age were taken into account, patients with depression were found to be 3.24 times more likely to be diagnosed with Parkinson’s than those without.

Even when researchers excluded the records of patients who were diagnosed with Parkinson’s shortly after their depression diagnosis, the link was still apparent suggesting that depression raises the risk of Parkinson’s over the long term.

In a joint announcement, three French Ministers expressed their support for people with dementia and their carers on World Alzheimer’s Day.

Marisol Touraine (Social Affairs and Health Minister), Geneviève Fioraso (Minister for Higher Education and Research) and Michèle Delaunay (Minister for the Elderly and Autonomy) also provided an update on the progress of the new “Neurodegenerative Plan”. This will be the continuation of France’s pioneering Plan Alzheimer.

Following the evaluation of the 3rd Plan Alzheimer (2008-2012) by Professors Joël Ankri and Christine Van Broeckhoven, four thematic working groups are being formed to identify the measures and actions of the new plan. The themes are:

  • improve diagnosis and early detection of the disease
  • respond to patients’ needs at each stage of the disease and in the entire country
  • increase awareness and conform to the highest standards of ethics, quality and welfare
  • increase the quantity and quality of research.

The new Neurodegenerative plan is expected to be finalised in the first quarter of 2014.

Highlights EU support for the coordination of national research efforts through the joint programming initiative on neurodegenerative diseases

More research, innovation and awareness is the solution to overcoming the societal challenges presented by dementia, argues Máire Geoghegan-Quinn.

Professor Leonard Van Den Berg, coordinator of the JPND-supported SOPHIA project, gave a brief insight into current progress on this biomarker project

Read more about the SOPHIA Project here. 

What are your key project achievements to date?

At this moment, the key project objective is to finalise development of the web-based platform including a virtual biobank to integrate the core clinical dataset from patients from all participating centres with biomarker data obtained from different biosamples. The core clinical dataset has been defined and the required fields for data collection of neuropathology biomarkers, wet biomarkers (in CSF, blood) and imaging biomarkers (MRI, MUNIX) are being set up. Standard Operating Procedures (SOPs) for sample collection and biomarker measurement have already been developed for some of the biomarkers. Other SOPs are still work in progress using the results from variability and reliability analysis on small sample datasets. The SOPs will also include a monitoring and quality control mechanism. Longitudinal data will be collected and analysed once the system is up and running. In the future new biomarkers can be quickly optimized and/or harmonized using a standard approach, if required.

Recently it became clear that the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) would be an excellent addition to the core clinical dataset that is collected from ALS patients: Collecting longitudinal reliable neuropsychology data would be useful to detect the specific profile of cognition and behaviour changes in ALS and to differentiate it from other disorders. Using the SOPHIA consortium, developers of ECAS are able to roll out and validate the screen throughout Europe within a short timeframe. The establishment of a consortium like SOPHIA has been instrumental to this effort, and will be just that for future biomarkers.

Where is the SOPHIA consortium making a real difference?

The European ALS community has established an active consortium ( www.ENCALS.eu) which holds several 2-3 day workshops per year among others about European collaboration on databases/biobanks, molecular biomarkers, and neuroimaging, and members have generated a series of consensus statements and standard operating procedures for biomarkers. These types of initiatives are an excellent foundation for European collaboration but more focused projects and funding is required for larger international collaborations to obtain the numbers of samples necessary to perform large biomarker validation studies in ALS and other motor neuron diseases. This is where the SOPHIA consortium is making the difference, as the results of its works will be a common European strategy for the prioritization and selection of candidate biomarker domains for optimization and harmonization and a permanent interactive European ALS biomarker tool for all researchers to enable optimization/harmonization of novel biomarkers using an integrated and robust pan-European ALS methodology.

In your opinion, what is the added-value of JPND support for this project?

The benefit of JPND support for the SOPHIA project lies in communication of project results to the wider ND disease society, which is essential for sharing all methods, database, biomarker essays, and biomarkers in SOPHIA with other members of the scientific community devoted to ALS and to other neurodegenerative diseases. The concept of this project (pan-European SOPs) can be expanded to other neurodegenerative disease areas resulting in a driving force for shared biomarker research.

What has been your experience of this research collaboration to date?

One year into the project it is very clear that this is a group of highly motivated investigators, keen to set up a platform to promote biomarker research for neurodegenerative diseases. All involved feel this can only be truly accomplished at a European level and are therefore eager to collaborate. Each partner in the project is actively involving his/her colleagues in order to make sure they have the right people working on each of the different sub-projects. This has been very helpful in progressing the tasks that the consortium has set itself and will result in deliverables of high standard.

The SOPHIA project website is available at http://www.sophiaproject.eu