User:Kmontine/Pacific Northwest Udall Center

Pacific Northwest Udall Center (PANUC) is a Morris K. Udall Center of Excellence for Parkinson's Disease Research [ref] at the University of Washington.

Udall Parkinson’s Disease Center funded by the National Institute of Neurologic Disease and Stroke. The Pacific Northwest Udall Center (PANUC) of Excellence in Parkinson's Disease is a collaborative effort among physicians and scientists at the University of Washington and Oregon Health & Sciences University to investigate cognitive impairment and dementia in Parkinson's disease. Core functions are highly patient-oriented with the goals of clinical service, improving diagnostic tools, and expanding opportunities to participate in clinical research. Three research projects span novel transgenic models, genetic risk factors, and patient studies of the bases of cognitive impairment in Parkinson's disease. Dr. Montine is the Principal Investigator of this five-year $10 million project.

PANUC (rhymes with Nanook)

Udall Centers http://www.ninds.nih.gov/research/parkinsonsweb/udall_centers/index.htm

Director: Thomas J. Montine, MD, Ph.D. Title: Pacific Northwest Udall Center (PANUC) Website: http://www.pathology.washington.edu/research/centers/Udall/

Central Theme The central theme for the Pacific Northwest Udall Center (PANUC), established in 2009, is cognitive impairment in Parkinson’s disease (PD). The PANUC will investigate and elucidate the mechanisms that underlie cognitive impairment in PD. In addition to generating new discoveries, the Center will develop novel resources for clinical, translational, and basic science researchers studying cognitive impairment in PD.

Center Structure http://www.ninds.nih.gov/research/parkinsonsweb/udall_centers/PANUC.htm Research Projects: Project 1 (R Palmiter, PI), “Functional and anatomical analysis of dopaminergic projections that mediate cognition”. This project will use a combination of genetically engineered mice and virus-medicated gene transfer to examine neural circuits that may underlie cognitive impairment in PD. Two novel transgenic mouse lines will be used to examine the behavioral effects of the loss of dopamine signaling through loss of signaling or neuronal death. Project 2 (TJ Montine, PI), “Selective and restricted denervation in Parkinson’s disease with cognitive impairment”. The first two aims of this project will use human brain autopsy from non-demented elderly with or without PD-associated pathology to examine the relationship of neurochemical and morphological (e.g. spiny neuron dendritic degeneration) alterations to cognitive impairment. The third aim will examine morphological consequences of dopamine denervation in the mouse model developed in Project 1. Project 3 (C Zabetian, PI), “Genetic risk factors for cognitive impairment in Parkinson’s disease”. This project will examine the association between gene variations linked to PD and cognitive impairment (microtubule associated protein tau, alpha-synuclein, apolipoprotein E) and the development and rate of decline of cognitive impairment in PD. This project will also examine the association of these genetic variations with CSF biomarker levels. Linked RO1: R01AG033398 (J Zhang PI), “Post-translational modifications of proteins in Parkinson’s disease ”. This project will examine novel protein modifications, e.g. phosphorylation, oxidation, and glycosylation, that might be important in PD pathogenesis as well as in assisting with PD diagnosis and monitoring disease progression, including development of cognitive impairment in PD. The project is intimately associated with Project 3 as well as multiple Cores. PANUC Cores: The Center is comprised of four Cores: Administrative (Core A, TJ Montine PI), Clinical (Core B, JB Leverenz PI), Genetics/Biomarker/Neuropathology (Core C, J Zhang PI), and Data Management and Biostatistics (Core D, K Edward PI). Twenty percent of the workload for Core B will be subcontracted to Oregon Health and Sciences University (Site PI, J Quinn). Core B will focus on the recruitment and characterization of two PD subject samples. The first, Clinical Sample (CS), will be a large (600 subjects) sample designed to allow the examination of genetic factors for cognitive impairment in PD (Project 3, C Zabetian, PI). The CS will undergo a limited motor and cognitive evaluation and blood draw for DNA and biomarkers twice during the initial five-year funding cycle of the PANUC. The second, Annual Sample (AS), will be a smaller (150 subjects) sample of PD patients that will undergo a more extensive characterization. This will include more detailed motor and cognitive evaluation on an annual basis. In addition to blood draw for DNA and biomarkers, these subjects will undergo lumbar puncture for cerebrospinal fluid (CSF) biomarker studies and will be asked to participate in the autopsy protocol. The AS will be an important source of material for Project 2 (TJ Montine, PI) and a linked biomarker RO1 (J Zhang, PI). Core C will be repository for collected blood, CSF, and autopsy material. This Core will also perform a standardized set of evaluations for genetic markers, blood and CSF biomarker measurements, and neuropathologic characterization of brain autopsy material. Core D will maintain a database for Cores B and C and be responsible for transmitting data collected to the PD-DOC. It will also be an important resource for study design and statistical analysis. The PANUC will bring together a multidisciplinary group of investigators focused on improving our understanding of cognitive impairment in PD. Projects within the Center and already linked to the Center will provide important insights into the pathophysiology of cognitive impairment in PD. Equally important, the PANUC will be an invaluable resource for other investigators interested in the study of PD, including those in other Udall centers. This will include blood, CSF, and tissue from extensively characterized subjects with PD.

Public Health Statement The PANUC is a multi-centered and multidisciplinary program designed to study the cognitive impairment observed in Parkinson’s disease (PD). While PD is typically known for its motor symptoms (tremor, slowness of movement), it is increasingly recognized that cognitive impairment, including dementia, can occur in PD. In fact, up to 80% of PD patients may eventually develop dementia. It is now recognized that this “non-motor” problem is linked to increased disability in the PD patient, is more stressful to caregivers of PD patients than the typical motor symptoms, and is associated with a shortened lifespan. Unfortunately, while there are excellent treatments for the motor symptoms of PD, there are very limited treatment options for cognitive impairment in PD. In large part that is due to a poor understanding of the causes of this problem in PD. The PANUC will address this limitation through the study of PD patients and through the development of models to better understand what brain changes lead to cognitive impairment. A better understanding will lead to better treatments for this significant problem in PD patients. NINDS Parkinson's Disease Information Page http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm

WPDR – wiki The Washington State Parkinson Disease Registry (WPDR) was created in May 2007 to facilitate Parkinson disease research by maintaining a list of people in Washington state with Parkinson disease interested in participating in Parkinson disease research[1] . Parkinson disease researchers request the WPDR notify its members of a research opportunity. The WPDR executive board then evaluates the requesting researcher's study protocol and notifies suitable registry members of the research opportunity. The intent of the registry is to increase membership in high quality Parkinson disease research while reducing the time and money necessary to recruit interested subjects. The Washington State Parkinson Disease Registry is sponsored by the Washington State Department of Health, a group of Washington state physicians at the University of Washington Department of Neurology and Parkinson disease advocacy groups including the Washington State chapter of the American Parkinson Disease Association, Northwest Collaborative Care, Northwest Parkinson's Foundation and Parkinson's Resources of Spokane Parkinson’s disease genetics research group

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