Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease affecting -1,000,000 Americans. PD begins about the 6* decade with onset of bradykinesia, rigidity, and resting tremor. In addition, non-motor symptoms occur at any stage of PD, and >80% of PD patients develop dementia (PDD) with disease progression. Cognitive impairment (CI), executive dysfunction and dementia add to the burden of PD and increase mortality, but the underlying basis of dementia in PD is unclear, and there are no effective disease modifying therapies. Despite significant research advances, the exact causes of PD/PDD/DLB are unknown. To address these issues, a National Institute of Neurological Disorders and Stroke Morris K. Udall Parkinson's Disease Research Center of Excellence (Udall Center) was launched at the Perelman School of Medicine (Penn) of the University of Pennsylvania in 2007. The competing renewal for years 6-10 of the Penn Udall Center builds on its recent progress to elucidate the progression of PD from normal cognition to cognitive impairment (CI), executive dysfunction and dementia in PDD, as well as disease progression in DLB in addition to the central nervous system (CNS) degeneration mediated by progressive accumulations of pathological alpha-synuclein (a-syn). Because recent Penn Udall Center studies raise the provocative, but highly plausible possibility that the progression of PD/PDD/DLB is linked to the cell-to-cell spread of pathological a-syn, the overarching goals of the Penn Udall Center are to elucidate mechanisms of disease progression and a-syn transmission through synergistic collaborations between basic and translational research Projects that work with each of the Cores to implement the mission of the Penn Udall Center in the renewal period. To that end, the Udall Center renewal will implement the following Cores and Projects: Administrative Core A: Core Leaer (CL) - J.Q. Trojanowski;Clinical Core B: CL - H. Hurtig;Co-CL - A Siderowf;Neuropathology, Biomarker and Genetics Core C: CL - J.Q. Trojanowski;Co- CL - y. Van Deerlin;Co-Investigator (Col) - EB. Lee;Data Management, Biostatistics and Bioinformatics Core D: CL - S. Xie;Co-I - Li-San Wang;Project I: "A Multimodal Biomarker Approach to Evaluating and Predicting Cognitive Decline in Lewy Body Spectrum Disorders": Project Leader (PL) - A. Siderowf;Co-I - A. Chen-Plotkin;Project II: "Mechanisms Of PD Executive Dysfunction In Language": PL - M. Grossman;Co-I - R. Gross;Project III: "Mechanisms Of Transmission Of Pathological Alpha-synuclein In Neurons": PL - V.M.-Y. Lee;Project IV: "Immune Therapy To Block PD Transmission In Mice": PL - J.Q. Trojanowski;Co-I - V.M.-Y. Lee and Kelvin Luk.
of the Penn Udall Center is that it elucidates mechanisms of CI, executive dysfunction and dementia in PD/PDD/DLB as well as mechanisms of neurodegeneration in these disorders mediated by the transmission of a-syn pathologies. By using new approaches and model systems to achieve its goals, the Penn Udall Center will elucidate novel disease mechanisms in PD/PDD/DLB and advance efforts to develop new interventions and better diagnostics for these disorders.
|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|
Showing the most recent 10 out of 105 publications