2004 — 2008 |
Mckeel, Daniel W |
P01Activity Code Description: For the support of a broadly based, multidisciplinary, often long-term research program which has a specific major objective or a basic theme. A program project generally involves the organized efforts of relatively large groups, members of which are conducting research projects designed to elucidate the various aspects or components of this objective. Each research project is usually under the leadership of an established investigator. The grant can provide support for certain basic resources used by these groups in the program, including clinical components, the sharing of which facilitates the total research effort. A program project is directed toward a range of problems having a central research focus, in contrast to the usually narrower thrust of the traditional research project. Each project supported through this mechanism should contribute or be directly related to the common theme of the total research effort. These scientifically meritorious projects should demonstrate an essential element of unity and interdependence, i.e., a system of research activities and projects directed toward a well-defined research program goal. |
Core--Neuropathology Core
The Healthy Aging and Senile Dementia progam project Neuropathology Core C has the Specific Aims of: (1) Assigning final neuropathologic diagnoses to all HASD subjects who come to autopsy (goal 25 new brains per year); (2) Performing brain autopsies on HASD subjects who give permission to do so, and to collect, store and distribute postmortem cerebrospinal fluid (CSF) and frozen brain tissue to program and other approved investigators to support research; (3) Maintaining electronic databases of neuropathology information that relates to autopsy examination, diagnosis, and tissue banking, in coordination with the Clinical and Biostatistics Cores; (4) Detecting and quantifying the full range of neuropathologic lesions associated with preclinical and overt dementia (senile plaques, neurofibrillary tangles, neuropil threads, argyrophilic grains, Lewy pathology, neuron loss, synaptic loss, tauopathic lesions, gliosis, etc.); and (5) to conduct developmental research using new histopathologic markers to promote diagnosis and to provide mechanistic insight into the causes and expression of dementing disorders compared to normal healthy aging and nondemented persons with preclinical Alzheimer disease (preclinical AD) brain lesions. * The Core leader McKeel, assisted by Senior Investigator Price and a well trained technical staff, have equipped the laboratory to process fixed brain tissue into paraffin blocks, to section these blocks at 6-10 microns, and to stain them with a variety of routine and special stains that include three silver methods (including Gallyas), thioflavine S, axon (modified Bielschowsky), and myelin stains (LFB-PAS). Immunohistochemical techniques are in place to detect a-beta amyloid, PHF type hyperphosphorylated tau, an Abeta-PHFtau dual stain to identify neuritic plaques with certainty, alpha-synuclein for synapses and Lewy pathology (neurites, pale bodies, brainstem and cortical Lewy bodies), ubiquitin, GFAP for astrocytic intermediate filaments, NeuN for neuron labeling, and synaptophysin for synapses. Dr. Price's laboratory will prepare 50 micron frozen sections of cytoarchitectonically defined brain regions (hippocampus, entorhinal cortex, cingulate cortex, gyrus rectus) for neuron counting using the Zeiss C.A.S.T. system. * This Core directly supports Projects 1-4 through it's Specific Aims, especially Aims 1, 3 and 5. Core brain lesion data will complement data obtained by the Clinical, Psychometric and Neuroimaging Cores.
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0.958 |
2005 — 2009 |
Mckeel, Daniel W |
P50Activity Code Description: To support any part of the full range of research and development from very basic to clinical; may involve ancillary supportive activities such as protracted patient care necessary to the primary research or R&D effort. The spectrum of activities comprises a multidisciplinary attack on a specific disease entity or biomedical problem area. These grants differ from program project grants in that they are usually developed in response to an announcement of the programmatic needs of an Institute or Division and subsequently receive continuous attention from its staff. Centers may also serve as regional or national resources for special research purposes. |
Neuropathology
The main aims of the Neuropathology Core and its Tissue Resource (brain bank) component are: (1) to render final diagnoses on all ADRC research subjects who undergo autopsy based on the NIA-Reagan Institute guidelines (Neurobiol Aging Suppl S1-S2, 1997) together with Braak neurofibrillary pathology staging supplemented with stringent quantitative criteria that were developed at WUSM based on the 1985 NIA-Khachaturian consensus guidelines; (2) to collect, freeze, store, and distribute blood, plasma/serum, buffy coat DNA samples, and frozen CSF and CNS tissue collected at autopsy to WU and outside investigators in order to facilitate (funded) projects and pilot studies; (3) to maintain electronic databases of neuropathologic and Tissue Resource information in concert with the Clinical Core (Morris) to supplement the master information databases maintained by the Data Management Core (Miller) and the centralized NACC minimal database in Seattle; and (d) to carry out developmental research designed to advance diagnostic sensitivity and specificity of present and emerging brain markers in aging, Alzheimer's disease (AD) and related dementing disorders. Examples of current developmental research are the application of alpha-synuclein antibodies to detect and quantify Lewy and GCI-MSA pathology, development of a dual immunostain for a-beta and hyperphosphorylated tau proteins, and adapting tissue collection methods to support neurogenomic and proteomic analyses. Core leader McKeel heads the ADRC Tissue Committee, which assesses feasibility of research proposals that involve materials from the Tissue Resource. He is also a member of the ADRC Executive committee which approves proposals for scientific merit. McKeel consults with investigators using the Tissue Resource facility and supervises all tissue distribution on approved projects. The Core has extensively collaborated during the past five years. A current major undertaking is a NACC-sponsored collaboration among seven ADRCs to study the neuropathology of nondemented aging to better define preclinical AD; the Neuropathology Core is the central reference laboratory. The Core conducts weekly braincutting and microscopic case review conferences that are attended by medical and allied health students, residents, nurses and physicians. The Core maintains an "Alzheimer Tutorial" portion of the WUSM ADRC website that is widely used as a teaching resource. The Core leader is active nationally as head of the NACC Neuropathology Core Leaders subcommittee on Quality Assurance and Standards. McKeel leads the production of a Standardized Methods Manual for the QA/S committee.
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0.958 |