RISK FACTORS FOR MSA

很少有研究探讨MSA的决定因素。除年龄外，没有确定的危险因素。本建议的目标是采取第一步，使用病例对照方法确定与MSA相关的因素。我们的假设将不仅取决于对MSA的当前理解的调查，而且取决于其他老年神经退行性疾病的决定因素和发病机制的当前理论，特别是帕金森病（PD），与MSA一样，含有α -突触核蛋白的内含物。此外，神经退行性疾病的危险因素共享蛋白质聚集的更普遍的发现将被调查。这个应用程序的一个独特优点是使用

Few studies have explored the determinants of MSA. Apart from age, no risk factor has been definitively identified. The goal of this proposal will be to take the first step in identifying factors associated with MSA, using a case-control method. Our hypotheses will be determined not only by an investigation of current understandings about MSA, but also by current theories regarding the determinants and the pathogenesis of other late-life neurodegenerative diseases, particularly Parkinson's disease (PD), which, like MSA, has alpha-synuclein-containing inclusions. In addition, risk factors for neurodegenerative disorders sharing the more general finding of protein aggregation will be investigated. A unique advantage of this application is the use of a well-characterized population with clinically Probable MSA, who will be followed clinically and for some studied at autopsy. All cases (n = 175) and controls (n = 350) enrolled in Core A will participate in Project I. Four specific aims will be addressed: SA 1: To test the hypothesis that exposure to specific occupational or a vocational chemical exposure is associated with an increased risk of MSA; SA 2: To test the hypothesis that specific dietary factors have a direct effect on the risk of MSA; SA 3: To test the hypotheses that certain risk factors associated with PD or Alzheimer's disease (AD) alter the risk of MSA. Risk factors of interest include: use of tobacco, caffeine, alcohol, anti-inflammatory drugs (lower risk); head trauma, stimulant use (higher risk); SA 4:To determine whether there is familial aggregation of MSA or the symptoms of MSA, or of MSA and other neurodegenerative diseases (PD, AD, motor neuron disease). For each hypothesis, exposures believed to be causally associated with MSA are expected to be more common in persons with MSA than in controls. Hypothesis testing will use classical methods for univariate and multivariate analysis of case-control studies. We stress that these investigations constitute a necessary exploratory step in attempting to characterize the determinants of MSA.