Category Archives: Research News (General)

With several therapeutic approaches in development for Huntington’s disease, there is a need for easily accessible biomarkers to monitor disease progression and therapy response.

Researchers at Leiden University Medical Center in The Netherlands have discovered a panel of five genes whose expression in whole blood correlates with progression of Huntington’s disease.

In a study published in The European Journal of Human Genetics, the group reported that transcriptome analysis of 91 Huntington’s mutation carriers, about one third of whom were presymptomatic, and 33 controls yielded 167 differentially expressed genes. Twelve of the top 20 genes were validated using a different technique, and five of these proved significant in a smaller, independent cohort as well.

The authors suggest a first empiric formula predicting total motor score from the expression levels of our biomarker panel. Their data supports the view that peripheral blood is a useful source to identify biomarkers for Huntington’s disease and monitor disease progression in future clinical trials.

Belgian scientists have completed a study, reprogramming skin cells from three dementia patients into induced pluripotent stem cells (iPSCs) – immature cells that mimic stem cells taken from early-stage embryos. Their findings, which revealed a signalling pathway linked to frontotemporal dementia (FTD), are published in the January 13th 2015 edition of the journal, Stem Cell Reports.

Prof. Philip Van Damme, from the Leuven Research Institute for Neuroscience and Disease in Belgium, said: “Our findings suggest that signalling events required for neurodevelopment may also play major roles in neurodegeneration.

Treatment with a drug that suppressed the pathway, known as “Wnt”, restored the ability of neurons affected by the disease to develop normally. “Targeting such pathways…may result in the creation of novel therapeutic approaches for frontotemporal dementia”, Prof. Van Damme said.

The researchers found that iPSCs derived from the patients’ cells were unable to generate cortical neurons, the cell type most affected by FTD. Cortical neurons are the cells responsible for most of the brain’s complex higher activity enabling thought, perception and voluntary movement.

Co-author Dr Catherine Verfaillie, from the University of Leuven in Belgium commented that IPSC models could now be used to better understand dementia, and in particular FTD, which accounts for about half of dementia cases before the age of 60.

Source: Alzheimer Europe

Parkinson’s disease has an insidious onset and is diagnosed when typical motor features occur. Several motor and non-motor features can occur before diagnosis, early in the disease process.

This study aimed to assess the association between first presentation of several prediagnostic features in primary care and a subsequent diagnosis of Parkinson’s disease, and to chart the timeline of these first presentations before diagnosis.

8166 individuals with a first diagnosis of Parkinson’s disease and 46755 people without Parkinson’s disease were identified from The Health Improvement Network UK primary care database.

A range of prediagnostic features such as tremor, balance impairment, constipation, depression were detected by the study several years before diagnosis of Parkinson’s disease in primary care. These data can be incorporated into ongoing efforts to identify individuals at the earliest stages of the disease for inclusion in future trials and to help understand progression in the earliest phase of Parkinson’s disease.

Source: The Lancet

Some cases of Alzheimer’s disease progress quickly, mimicking prion-based Creutzfeldt-Jakob disease (CJD). Many people with this form of Alzheimer’s are misdiagnosed, because clinicians have no reliable way to distinguish between the two disorders.

In the January 5 JAMA Neurology, researchers led by Isabelle Quadrio at Hospices Civils de Lyon, Bron, France, propose using levels of total prion protein (t-PrP) in cerebrospinal fluid (CSF) to differentiate CJD from AD. The authors found that people with prion disease had lower CSF levels of this protein than AD patients did. In a study of 209 patients with either disorder, t-PrP classified patients much more accurately than the currently accepted biomarker, 14-3-3 protein, they report. When they combined t-PrP with CSF tau, they correctly identified 96 percent of patients with atypical, fast-progressing AD in this study, as compared with 57 percent using 14-3-3 alone.

Source: AlzForum

The personal genetics company 23andMe, Inc. has announced an agreement with Genentech, a member of the Roche Group, to generate whole genome sequencing data for approximately 3,000 people in 23andMe’s Parkinson’s disease community. The goal of the collaboration is to identify new therapeutic targets for treating Parkinson’s disease.

Source: 23andMe (Press Release)

The Dementia in Europe Yearbook 2014, produced by Alzheimer Europe is a comparative report on care pathways for people with dementia living at home in Europe.

The pathways to get a diagnosis of dementia are complex and are likely to be multifactorial. Many people living with dementia in Europe are still not diagnosed, and often the diagnosis comes too late. Every person with dementia has the right to a high quality, timely diagnosis, if they so wish. There is now clear indication that people can live well with dementia. Nevertheless, without the right support and care this may not be possible. Getting the necessary support and care depends on several factors. Among them, availability and appropriateness are key, as are the informational aspects and the navigability of the complex health and care systems involved in the diagnosis and care of people with dementia.

This comparative report contains information on national policies and practices addressing different aspects of the timely diagnosis of dementia and of the post-diagnostic care and support available to individuals living with dementia in 30 European countries. The report outlines the main similarities and differences in the processes that people need to follow to be diagnosed and to access the support and care in these countries. It also highlights some of the gaps and main challenges that these individuals may experience. In doing so, the report shows that there is not always a single, linear pathway that may suit every person and every country.

The Dementia in Europe Yearbook 2014 is available for free download on the Alzheimer Europe website.

Source: Alzheimer Europe

Age-related neurodegenerative disorders including Alzheimer’s disease and Huntington’s disease (HD) consistently show elevated DNA damage, but the relevant molecular pathways in disease pathogenesis remain unclear. One attractive gene is that encoding the ataxia-telangiectasia mutated (ATM) protein, a kinase involved in the DNA damage response, apoptosis, and cellular homeostasis. Loss-of-function mutations in both alleles of ATM cause ataxia-telangiectasia in children, but heterozygous mutation carriers are disease-free. Persistently elevated ATM signaling has been demonstrated in Alzheimer’s disease and in mouse models of other neurodegenerative diseases.

This new study shows that ATM signaling was consistently elevated in cells derived from HD mice and in brain tissue from HD mice and patients. ATM knockdown protected from toxicities induced by mutant Huntingtin (mHTT) fragments in mammalian cells and in transgenic Drosophila models.

By crossing the murine Atm heterozygous null allele onto BACHD mice expressing full-length human mHTT, the researchers show that genetic reduction of Atm gene dosage by one copy ameliorated multiple behavioral deficits and partially improved neuropathology. Small-molecule ATM inhibitors reduced mHTT-induced death of rat striatal neurons and induced pluripotent stem cells derived from HD patients.

The study provides converging genetic and pharmacological evidence that reduction of ATM signaling could ameliorate mHTT toxicity in cellular and animal models of HD, suggesting that ATM may be a useful therapeutic target for HD.

Source; Science Magazine

A new study entitled “Evaluating the relationship between amyloid-β and α-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson’s disease” reports a correlation between α-synuclein and amyloid-β in the brain of patients affected by neurodegenerative diseases, such as Parkinson’s disease. The study was published in the journal Alzheimer’s Research &Therapy.

In this study, the authors measured both soluble and insoluble amyloid-β and α-synuclein in human post-mortem brain tissue and analyzed whether there is a relation between the levels of amyloid-β, total α-synuclein, pSer129 α-synuclein and cognitive function ante-mortem in Parkinson’s disease patients. Their main findings were the discovery of a positive correlation between the levels of insoluble pSer129 α-synuclein with insoluble and soluble amyloid-β protein in most brain regions analyzed. The correlation was significantly higher in Parkinson’s disease and dementia with Lewy bodies patients when compared to controls. Additionally, the authors found that the proportion of α-synuclei phosphorylated at Ser129 correlated with ante-mortem mini-mental state examination.

Their findings establish a pathogenic link between the accumulation of amyloid-β and the phosphorylation of Ser129 at α-synuclein, thus increasing disease severity and the probability of developing dementia. The authors highlight that additional studies are required to understand fully how the interaction is maintained.

Source: Alzheimer’s News Today

Marisol Touraine, Minister of Social Affairs, Health and Women’s Rights, Geneviève Fioraso, State Secretary for Higher Education and Research, and Laurence Rossignol, Secretary of State for Families, People elderly and Autonomy, recently launched the French National Plan neurodegenerative diseases 2014-2019.

Announced by the President of the Republic, this plan from a wide consultation with stakeholders, has three priorities:

Improving the diagnosis and management of patients
Ensuring the quality of life of patients and their caregivers
Develop and coordinate research

The French Government is committed to a dynamic of progress in research, care and support. The plan takes into account the specificities of each disease and provides concrete solutions to the needs of patients and their caregivers.