New Genetic Cause Of Alzheimer's Disease Discovered

Researchers from the Flanders Interuniversity Institute for Biotechnology (VIB) connected to the University of Antwerp are the first to show that the quantity of amyloid protein in brain cells is a major risk factor for Alzheimer's disease. Amyloid protein has already been known to be the primary component of the senile plaques in the brains of patients. The new discovery demonstrates that the greater the quantity of the protein that is produced, the younger the dementia patient is. Alzheimer's disease Alzheimer's disease is a memory disorder that affects up to 70% of all dementia patients. In Belgium, about 100,000 people suffer from this disease. The disease gradually destroys brain cells in the deep areas of the brain that are responsible for memory and knowledge. Ever since the disease was first reported by Alois Alzheimer - 100 years ago now - scientists have been searching diligently for ways to treat it. Amyloid plaque formation plays a key role Genetic research has previously shown a direct connection between amyloid protein and the development of senile plaques and loss of cells. Amyloid protein originates when it is cut by enzymes from a larger precursor protein. In very rare cases (fewer than 1 in 1000 patients), mutations appear in that amyloid precursor protein, causing it to change shape and be cut differently. The amyloid protein that is formed now has different characteristics, causing it to begin to stick together and precipitate as amyloid plaques. The development of amyloid plaques in the brain tissue of Alzheimer patients is a central factor in the search for a therapy for Alzheimer's disease. A lot or not much of the amyloid precursor protein is a risk factor The fact that patients with Down syndrome get Alzheimer's disease shows that the quantity of the amyloid precursor protein contributes to the disease: in fact, patients with Down syndrome have 3 copies of the gene (or hereditary code) for the amyloid precursor protein and therefore produce 150% instead of 100% of the protein. So, Jessie Theuns and her colleagues, under the direction of Christine Van Broeckhoven, hypothesized that the quantity of amyloid precursor protein might also play a role in Alzheimer's disease. The geneticists from Antwerp systematically studied the hereditary code that is responsible for controlling the expression of the gene (= promoter). Biological processes in our body are strictly regulated, primarily by closely controlling the amount of each protein that is produced. The promoter of a gene has the most important control function in this process. In younger Belgian and Dutch Alzheimer's patients (younger than 70), the researchers found genetic variations in the promoter that increased the gene expression and thus the formation of the amyloid precursor protein. These variations in the promoter that increase expression occur up to 20 times more frequently (2 per 100 patients) than the mutations in the precursor protein that change the shape. Furthermore, there is a connection with the age at which the symptoms are first detected: the higher the expression (up to 150% as in Down syndrome), the younger the patient (starting between 50 and 60 years of age). Thus, the amount of amyloid precursor protein is a genetic risk factor for Alzheimer's disease in the ageing process. Prospects for tests and treatments These new findings lead to a new understanding: namely, that the quantity of the amyloid precursor protein, and thus of the amyloid protein, in brain cells contributes significantly to the risk of contracting Alzheimer's. This discovery will have to be taken into account in diagnostic tests and in the search for new medicines. http://www.medicalnewstoday.com/medicalnews.php?newsid=41965 Scientists Develop New Concept With Potential To Help Predict How Individuals May Respond To Drugs Scientists from Imperial College London and Pfizer have developed a new method that could predict individual patient responses to drug treatments. The authors anticipate that the development will advance biomedical research further towards development of personalised medicines. Research published today in Nature demonstrates the new 'pharmaco-metabonomic' approach that uses a combination of advanced chemical analysis and mathematical modelling to predict drug-induced responses in individual patients. The method is based on analysis of the body's normal metabolic products, metabolites, and metabolite patterns that are characteristic of the individual. The authors hypothesize that these individual patterns can be used to diagnose diseases, predict an individual's future illnesses, and their responses to treatments. Not all drugs are effective in all patients and in rare cases adverse drug reactions can occur in susceptible individuals. To address this, researchers from Imperial College and Pfizer have been exploring new methods for profiling individuals prior to drug therapy. The new approach, if successful, requires the analysis of the metabolite profiles of an individual from a urine, or other biofluid, sample. The researchers tested their approach by administering paracetamol to rats and measuring how it affected their livers and how it was excreted. Before giving the dose they measured the levels of the natural metabolites in the rats' urine. Metabolites being small molecules produced by normal body functions, they can indicate a body's drug response. After creating a 'pre-dose urinary profile' for each rat, the researchers used computer modelling to relate the nature of the pre-dose metabolite profile to the nature of the post-dose response. Professor Jeremy Nicholson, from Imperial College London, who led the research, says: "This new technique is potentially of huge importance to the future of healthcare and the pharmaceutical industry. The 'pharmaco-metabonomic' approach is able to account for genetic as well as many environmental factors, and other important contributors to individual health such as the gut microfloral activity. These factors strongly influence how an individual absorbs and processes a drug and also influence their individual metabolism, making this new approach the first step towards the development of more personalised healthcare for large numbers of patients." The discovery of this new technology for predicting responses to drugs, which is not limited to individual genetic differences, will hopefully be a key component in the pharmaceutical industry's aim to understand how patients might benefit from more individualised therapies. The new method is expected to be synergistic with existing pharmacogenomic approaches. The new methodology is in early stage of development and will be studied in humans to evaluate its possible clinical application. The researchers hope this new technique might one day allow doctors to personalise drug treatments for some individuals, providing physicians with the ability to prescribe medicines that will be most effective for certain patient groups, and at a tailored dose-range for maximum efficacy and safety. "Source":[ http://www.medicalnewstoday.com/medicalnews.php?newsid=41962].

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