Neuropathology Core C The Neuropathology Core (Core C) of the Johns Hopkins Udall Parkinson's Disease Research Center has three overarching goals. The first is to conduct postmortem neuropathological assessments in subjects from the Clinical Core and to distribute autopsy brain tissues for research to Projects 1, 2 &4 and the Proteomic Core. The second is to obtain a comprehensive genetic profile of all the postmortem tissues available in the Udall Center collection. The third is to provide support for the morphological evaluation of genetically engineered mouse models by investigators in Projects 1, 2 &4.
The specific aims of Core C are as follows: (1) to arrange and perform neuropathological autopsies of cases of Parkinson's disease (PD) and Lewy body disease (LBD), and control subjects followed by the Clinical Core, and to formulate pathological diagnoses; (2) to accession, prepare, catalog, and assist in the analysis of human postmortem tissues from cases of PD/LBD and related disorders, as well as age-matched and also younger controls for studies proposed in Projects 1, 2 &4 and the Proteomic Core;(3) to characterize the molecular genetic profiles of PD/LBD postmortem tissues available in the BRC through a collaboration with the Laboratory of Neurogenetics at NIA (A. Singleton, Ph.D.);and (4) to use CLARITY technology for preparation of mouse brain tissues in support of studies delineated in Projects 1, 2 &4. Despite recent advances in neuroimaging postmortem brain examination remains indispensable. For accurate diagnosis of PD (Parkinson's disease) and LBD (Lewy body disease) in our experience, ~20% of cases clinically diagnosed as PD have other etiologies, and >30% of the cases have coexisting morbidities. Moreover, since autopsies are the essential source of tissues for studying molecular/biochemical abnormalities of the human brain associated with PD/LBD, a thorough pathological characterization is important before tissues can be used in studies proposed in Projects 1, 2 &4 and by the Proteomic Core. Core C is expanding its postmortem tissue collection to include a large number of specimens from younger subjects (16 to 65 years) suitable to examine the very early stages of PD/LBD pathology and its pathogenesis. These tissues are accessioned through collaboration with the Lieber Institute for Developmental Disorders at Johns Hopkins. Finally, by using CLARITY, a state-of-the-art morphological technique implemented by Core C, investigators in Projects 1, 2 &4 will be able to produce translucent preparations of whole mouse brains that allow interrogation of molecular events not only of single neuronal populations but of networks relevant to PD and LBD.

Public Health Relevance

The Morris Udall Center for Parkinson's Disease Research of the Johns Hopkins University is an integrated program aimed at finding improved treatments for patients with Parkinson's disease and Lewy body diseases. Complimentary activities within the center include clinical and basic research studies that incorporate state- of-the art methodologies, and contribute significantly to national programs. Specifically, Core C will conduct neuropathological autopsies, formulate diagnoses, and prepare and distribute post-mortem brain tissues for research to investigators at JHU Udall Center and extramurally, collaborate on the genetic profiling of a large collection of post-mortem PD/LBD tissues accrued over the last fifteen years, and provide support to basic research projects on state-of-the-art morphological approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
2P50NS038377-16
Application #
8882843
Study Section
Special Emphasis Panel (ZNS1-SRB-J (07))
Project Start
Project End
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
16
Fiscal Year
2014
Total Cost
$283,500
Indirect Cost
$108,500
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Mills, Kelly A; Mari, Zoltan; Bakker, Catherine et al. (2016) Gait function and locus coeruleus Lewy body pathology in 51 Parkinson's disease patients. Parkinsonism Relat Disord 33:102-106
Mao, Xiaobo; Ou, Michael Tianhao; Karuppagounder, Senthilkumar S et al. (2016) Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science 353:
Geiger, Joshua T; Arthur, Karissa C; Dawson, Ted M et al. (2016) C9orf72 Hexanucleotide Repeat Analysis in Cases with Pathologically Confirmed Dementia with Lewy Bodies. Neurodegener Dis 16:370-2
Mata, Ignacio F; Leverenz, James B; Weintraub, Daniel et al. (2016) GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease. Mov Disord 31:95-102
Rosenthal, Liana S; Drake, Daniel; Alcalay, Roy N et al. (2016) The NINDS Parkinson's disease biomarkers program. Mov Disord 31:915-23
Jo, Junghyun; Xiao, Yixin; Sun, Alfred Xuyang et al. (2016) Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons. Cell Stem Cell 19:248-57
Karuppagounder, Senthilkumar S; Xiong, Yulan; Lee, Yunjong et al. (2016) LRRK2 G2019S transgenic mice display increased susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurotoxicity. J Chem Neuroanat 76:90-97
Davis, Marie Y; Johnson, Catherine O; Leverenz, James B et al. (2016) Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA Neurol 73:1217-1224
Nucifora Jr, Frederick C; Nucifora, Leslie G; Ng, Chee-Hoe et al. (2016) Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. Nat Commun 7:11792
Mills, Kelly A; Mari, Zoltan; Pontone, Gregory M et al. (2016) Cognitive impairment in Parkinson's disease: Association between patient-reported and clinically measured outcomes. Parkinsonism Relat Disord 33:107-114

Showing the most recent 10 out of 206 publications