The Neuropathology, Biomarker and Genetics Core C of this new National Institute of Neurological Disorders and Stroke (NINDS) Morris K. Udall Parkinson's Disease Research Center of Excellence (Udall Center) at the University of Pennsylvania School of Medicine (Penn) will acquire, preserve and characterize postmortem brain tissue in addition to biological samples collected antemortem from clinically assessed Parkinson's disease (PD) patients without and with cognitive impairments (CI), executive dysfunction and dementia (PDD) as well as dementia with Lewy body (DLB) patients and controls followed in Core B. PD, PDD and DLB represent a spectrum of overlapping neurodegenerative disorders known as alpha-synucleinopathies that are characterized by prominent filamentous alpha-synuclein (a-syn) aggregates mainly in neurons or their processes that are referred to as Lewy bodies (LBs) and Lewy neurites (LNs), respectively. Since emerging data suggest progression of PD/PDD/DLB could result from the cell-to-cell spread of pathological a-syn strains in the central nervous system followed by progressive neurodegeneration, efforts to understand the progression of PD to CI, executive dysfunction and dementia (Projects I/II) and mechanism of the cell-to- cell spread of pathological a-syn (Projects III/ IV) are the focus of the Penn Udall Center in the renewal period. Core C supports these goals by implementing postmortem diagnostic criteria for PD/PDD/DLB using state-of-the-art methods while also assessing the utility of other antemortem diagnostics including studies of potential PD/PDD/DLB biomarkers and molecular genetic strategies. Thus, Core C will work closely with the other Cores and all of the Projects in the Penn Udall Center to play a critical facilitative role in the mission of this Center by improving current diagnostic methods, and providing samples of thoroughly characterized fresh, unfixed frozen and fixed brain tissues as well as DNA and biofluids to investigators in this and other Udall Centers for research.

Public Health Relevance

of Core C to the Penn Udall Center overall is that it uniquely supports the mission of the Center to elucidate mechanisms of CI, executive dysfunction and dementia in PD/PDD/DLB as well as mechanisms of neurodegeneration in these disorders mediated by a-syn pathologies. By partnering with the Cores/Projects using new approaches to achieve the Center's goals. Core C contributes to elucidating disease mechanisms in PD/PDD/DLB and efforts to develop novel interventions and better diagnostics for these disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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Special Emphasis Panel (ZNS1-SRB-J)
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University of Pennsylvania
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Kalia, Lorraine V; Lang, Anthony E; Hazrati, Lili-Naz et al. (2015) Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol 72:100-5
Swanson, Christine R; Li, Katherine; Unger, Travis L et al. (2015) Lower plasma apolipoprotein A1 levels are found in Parkinson's disease and associate with apolipoprotein A1 genotype. Mov Disord 30:805-12
Irwin, David J; McMillan, Corey T; Suh, EunRan et al. (2014) Myelin oligodendrocyte basic protein and prognosis in behavioral-variant frontotemporal dementia. Neurology 83:502-9
Luk, Kelvin C; Lee, Virginia M-Y (2014) Modeling Lewy pathology propagation in Parkinson's disease. Parkinsonism Relat Disord 20 Suppl 1:S85-7
Avants, Brian B; Libon, David J; Rascovsky, Katya et al. (2014) Sparse canonical correlation analysis relates network-level atrophy to multivariate cognitive measures in a neurodegenerative population. Neuroimage 84:698-711
Peelle, Jonathan E; Powers, John; Cook, Philip A et al. (2014) Frontotemporal neural systems supporting semantic processing in Alzheimer's disease. Cogn Affect Behav Neurosci 14:37-48
Cook, Philip A; McMillan, Corey T; Avants, Brian B et al. (2014) Relating brain anatomy and cognitive ability using a multivariate multimodal framework. Neuroimage 99:477-86
Ash, Sharon; Menaged, Anna; Olm, Christopher et al. (2014) Narrative discourse deficits in amyotrophic lateral sclerosis. Neurology 83:520-8
McCluskey, Leo; Vandriel, Shannon; Elman, Lauren et al. (2014) ALS-Plus syndrome: non-pyramidal features in a large ALS cohort. J Neurol Sci 345:118-24
Escobar, Valerie Drews; Kuo, Yien-Ming; Orrison, Bonnie M et al. (2014) Transgenic mice expressing S129 phosphorylation mutations in ?-synuclein. Neurosci Lett 563:96-100

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