Pilar Martinez-Martinez

Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease

The etiology of the sporadic form of Alzheimers disease (AD) remains largely unknown. Recent evidence has suggested that gene-environment interactions (GxE) may play a crucial role in its development and progression. Whereas various susceptibility loci have been identified, like the apolipoprotein E4 allele, these cannot fully explain the increasing prevalence of AD observed with aging. In addition to such genetic risk factors, various environmental factors have been proposed to alter the risk of developing AD as well as to affect the rate of cognitive decline in AD patients. Nevertheless, aside from the independent effects of genetic and environmental risk factors, their synergistic participation in increasing the risk of developing AD has been sparsely investigated, even though evidence points towards such a direction. Advances in the genetic manipulation of mice, modeling various aspects of the AD pathology, have provided an excellent tool to dissect the effects of genes, environment, and their interactions. In this paper we present several environmental factors implicated in the etiology of AD that have been tested in transgenic animal models of the disease. The focus lies on the concept of GxE and its importance in a multifactorial disease like AD. Additionally, possible mediating mechanisms and future challenges are discussed.

Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease (Erratum)

1 School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands 2 Department of Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA 3 Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK 4 Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany

AB026. PS01.08. Acetylcholine receptor antibody levels correlate with clinical status in myasthenic thymomas and non-thymomas

Background: There is no consensus about a correlation between clinical severity of disease and the levels of antiacetylcholine receptor antibody (AChR) in patients with myasthenia gravis (MG). Previous research showed no association with a follow up for several months. The aim of this 5-year-retrospective study was to investigate the possible correlation between the patients’ clinical symptoms and anti-AChR-levels measured with a specific quantitative immunoprecipitation assay (RIA). Methods: We retrospectively analyzed 50 patients with MG, who were treated at the Maastricht University Medical Center. Inclusion criteria were defined based on positive antiAChR-levels (>0.25 nmol/L) and the use of minimal one immunosuppressive therapy. The anti-AChR-levels were measured by RIA with serial serum dilutions (IBL, Germany). Clinical severity of disease was measured by using the Myasthenia Gravis Foundation of America (MGFA) protocol. We analyzed the MGFA-scores and anti-AChR-levels at onset of disease, and subsequently after 6 months, 1, 3 and 5 years. Results: Of the 50 included patients, 28 underwent a sternal or robotic thymectomy before or during the follow up. Pathological results showed 10 thymomas (20%). The mean anti-AChR-levels and the mean MGFA-score of the 50 patients significantly decreased continuously during follow up in both thymomas (P=0.025) and non-thymomas (P=0.011). No significantly differentiation in decrease of titer levels and MGFA was measured between thymomas and non-thymomas. A drop of 25% and 50% of the anti-AChR-levels was measured at a mean time of 21 and 32 months respectively. Conclusions: The correlation coefficient r =0.98 was found between clinical severity of disease and the decrease of antiAChR levels in MG patients with both thymomas and nonthymomas. No significantly differentiation in decrease of titer levels and MGFA was measured between thymomas and nonthymomas. On average it took more than 2 years to achieve a 50% reduction of anti-AChR-levels. Anti-AChR-levels are useful as a marker for the evaluation of immunotherapy and have to be followed for several years.