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biomarkers for Alzheimer’s disease  
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Summary for non-technicians
 
Background
Alzheimer’s disease is one of the most common causes of dementia. It currently affects 4 million subjects in the European Union. The prevalence of Alzheimer’s disease is expected to increase substantially the next decades due to the aging population. Alzheimer’s disease severely affects the quality of life of patients and their relatives. It also poses a major burden to the health care system.

The protein beta amyloid plays an important role in the development of the disease. Researchers hope to develop new drugs, which can modify the production of the beta amyloid protein such that the disease can be prevented or slowed down. However, it is still difficult to diagnose Alzheimer’s disease in an early stage. In addition, markers for the beta amyloid, protein which can be used to assess the efficacy of these drugs, are not yet available.

Aims of the study
Recent studies indicated that the beta amyloid protein in an oligomeric form play an important role in the early stage of Alzheimer’s disease. The aim of the present project is to investigate whether beta amyloid oligomers in cerebrospinal fluid and plasma can be used for the early diagnosis of Alzheimer’s disease and whether they can be used as a marker of treatment response. In addition, it will be investigated whether genes known to be involved in beta amyloid protein processing influence levels of the oligomers.

Study outline
Oligomers will be measured using two techniques. The first technique is based on an ultra sensitive immuno-polymerase chain reaction and will be developed during the project. The second technique is based on a combination of immunoprecipitation and ELISA and has already been developed by one of the partners. Measurements will be performed in cerebrospinal fluid and plasma samples of 100 subjects with Alzheimer’s disease, 250 subjects with mild cognitive impairment (a prodromal stage of Alzheimer’s disease), 100 subjects with other types of dementia, and 50 control subjects. In order to investigate the potential of beta amyloid oligomers to be used as marker of treatment response, cerebrospinal fluid samples and blood samples will be collected 9 and 18 months after baseline in 60 subjects with Alzheimer’s disease and 60 with mild cognitive impairment. The project started 1 January 2007.