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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS044233-02
Application #
7553781
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$196,537
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Rockenstein, Edward; Ostroff, Gary; Dikengil, Fusun et al. (2018) Combined Active Humoral and Cellular Immunization Approaches for the Treatment of Synucleinopathies. J Neurosci 38:1000-1014
Coon, Elizabeth A; Ahlskog, J Eric; Silber, Michael H et al. (2018) Do selective serotonin reuptake inhibitors improve survival in multiple system atrophy? Parkinsonism Relat Disord 48:51-53
Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G et al. (2018) Multiple system atrophy and apolipoprotein E. Mov Disord 33:647-650
Wenning, Gregor; Trojanowski, John Q; Kaufmann, Horacio et al. (2018) Is multiple system atrophy an infectious disease? Ann Neurol 83:10-12
Cutsforth-Gregory, Jeremy K; McKeon, Andrew; Coon, Elizabeth A et al. (2018) Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure. Mayo Clin Proc 93:1440-1447
Singer, Wolfgang; Berini, Sarah E; Sandroni, Paola et al. (2017) Pure autonomic failure: Predictors of conversion to clinical CNS involvement. Neurology 88:1129-1136
Valera, Elvira; Spencer, Brian; Mott, Jennifer et al. (2017) MicroRNA-101 Modulates Autophagy and Oligodendroglial Alpha-Synuclein Accumulation in Multiple System Atrophy. Front Mol Neurosci 10:329
Valera, Elvira; Spencer, Brian; Fields, Jerel A et al. (2017) Combination of alpha-synuclein immunotherapy with anti-inflammatory treatment in a transgenic mouse model of multiple system atrophy. Acta Neuropathol Commun 5:2
Coon, Elizabeth A; Fealey, Robert D; Sletten, David M et al. (2017) Anhidrosis in multiple system atrophy involves pre- and postganglionic sudomotor dysfunction. Mov Disord 32:397-404
El-Agnaf, Omar; Overk, Cassia; Rockenstein, Edward et al. (2017) Differential effects of immunotherapy with antibodies targeting ?-synuclein oligomers and fibrils in a transgenic model of synucleinopathy. Neurobiol Dis 104:85-96

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