The major goals of Core C are to support the research activities of this PPG by obtaining, characterizing, and distributing postmortem brain tissues from patients with MSA. The Core will provide detailed neuropathological data from these cases to Core and Project investigators, as well as provide advice and technical support to investigators in this PPG. These goals will be accomplished by the following specific aims: 1. To perform brain autopsies on PPG participants with clinical features of MSA in a timely fashion and according to standard protocol. 2. To provide detailed neuropathologic evaluation to establish a definitive diagnosis and to document the presence or absence of other central (CNS) and peripheral (PNS) nervous system pathologies. Neuropathologic data for all brains will be collected using standardized methods for gross dissection and neurohistology. These approaches include hematoxylin and eosin (H&E), myelin and silver stains, and The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and Braak scoring, in all cases. Additionally we will immunostain tissues with antibodies to a-synuclein. In cases with Lewy bodies (LB), LBs will be counted in cortical regions to assign a diagnostic category according to the Consortium for Dementia with Lewy Bodies criteria. We will assess the distribution and abundance of GCIs and related LB-like neuronal inclusions, dystrophic synuclein neurites, and other synuclein pathologies in the CNS and PNS of patients with MSA, compared to controls without MSA or any other neurological disease. 3. Collect cerebral spinal fluid (CSF), blood (huffy coat), and blood-spot samples on all cases. CSF and huffy coat samples will be frozen and banked for future research studies. 4. Store brain tissue and CSF, blood (buffy coat), and blood spot samples and provide pathologically well-characterized tissue samples for on-going research (Projects 2, 3, and Core D). 5. Monitor the acquisition and distribution of these tissue samples using a computerized database and maintain a computerized archive of histopathologic findings for research use by investigators in this PPG. 6. Provide advice and technical support to facilitate studies by PPG investigators on synucleinopathies and synucleinopathy models, especially Projects 2 and 3. 6. Prepare and store DNA from MSA patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS044233-10
Application #
8740564
Study Section
Special Emphasis Panel (ZNS1-SRB-E)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
10
Fiscal Year
2014
Total Cost
$91,579
Indirect Cost
$32,920
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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
Coon, Elizabeth A; Low, Phillip A (2017) Pure autonomic failure without alpha-synuclein pathology: an evolving understanding of a heterogeneous disease. Clin Auton Res 27:67-68
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
Spencer, Brian; Valera, Elvira; Rockenstein, Edward et al. (2017) Anti-?-synuclein immunotherapy reduces ?-synuclein propagation in the axon and degeneration in a combined viral vector and transgenic model of synucleinopathy. Acta Neuropathol Commun 5:7
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
Coon, Elizabeth A; Ahlskog, J Eric; Silber, Michael H et al. (2017) Do selective serotonin reuptake inhibitors improve survival in multiple system atrophy? Parkinsonism Relat Disord :
Spencer, Brian; Kim, Changyoun; Gonzalez, Tania et al. (2016) ?-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease. Hum Mol Genet 25:1100-15
Loavenbruck, Adam J; Singer, Wolfgang; Mauermann, Michelle L et al. (2016) Transthyretin amyloid neuropathy has earlier neural involvement but better prognosis than primary amyloid counterpart: an answer to the paradox? Ann Neurol 80:401-11
Spencer, Brian; Williams, Stephanie; Rockenstein, Edward et al. (2016) ?-synuclein conformational antibodies fused to penetratin are effective in models of Lewy body disease. Ann Clin Transl Neurol 3:588-606

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