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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
2P50NS053488-06
Application #
8435748
Study Section
Special Emphasis Panel (ZNS1-SRB-J (01))
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-06-30
Support Year
6
Fiscal Year
2012
Total Cost
$316,800
Indirect Cost
$118,800
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Shi, Min; Tang, Lu; Toledo, Jon B et al. (2018) Cerebrospinal fluid ?-synuclein contributes to the differential diagnosis of Alzheimer's disease. Alzheimers Dement 14:1052-1062
Tropea, Thomas F; Xie, Sharon X; Rick, Jacqueline et al. (2018) APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease. Mov Disord 33:289-297
Portelius, Erik; Olsson, Bob; Höglund, Kina et al. (2018) Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology. Acta Neuropathol 136:363-376
Polinski, Nicole K; Volpicelli-Daley, Laura A; Sortwell, Caryl E et al. (2018) Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson's Disease in Rodents. J Parkinsons Dis 8:303-322
Rey, Nolwen L; George, Sonia; Steiner, Jennifer A et al. (2018) Spread of aggregates after olfactory bulb injection of ?-synuclein fibrils is associated with early neuronal loss and is reduced long term. Acta Neuropathol 135:65-83
Lewczuk, Piotr; Riederer, Peter; O'Bryant, Sid E et al. (2018) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry 19:244-328
Simuni, Tanya; Caspell-Garcia, Chelsea; Coffey, Christopher S et al. (2018) Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson's disease: the PPMI cohort. J Neurol Neurosurg Psychiatry 89:78-88
Alcolea, Daniel; Irwin, David J; Illán-Gala, Ignacio et al. (2018) Elevated YKL-40 and low sAPP?:YKL-40 ratio in antemortem cerebrospinal fluid of patients with pathologically confirmed FTLD. J Neurol Neurosurg Psychiatry :
Luna, Esteban; Decker, Samantha C; Riddle, Dawn M et al. (2018) Differential ?-synuclein expression contributes to selective vulnerability of hippocampal neuron subpopulations to fibril-induced toxicity. Acta Neuropathol 135:855-875
Zee, Jarcy; Xie, Sharon X (2018) The Kaplan-Meier Method for Estimating and Comparing Proportions in a Randomized Controlled Trial with Dropouts. Biostat Epidemiol 2:23-33

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