2009 — 2013 |
Cairns, Nigel John |
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. |
Neuropathology
The aims of the HASD Neuropathology Core D and Brain Tissue Bank are: 1. To make neuropathologic diagnoses on all new brain accessions from HASD research subjects using standard diagnostic criteria where possible. Alzheimer's disease lesion severity will be quantified using the staging scheme of Braak and Braak (1991 and 2006). The neuropathologic diagnosis of Alzheimer's disease (AD) is based on NIA-Reagan Institute (1997), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD;1997), and Khachaturian (1985) criteria. The severity of Lewy body pathology will be assessed using the criteria of Braak et a/. (2003) and the diagnosis of dementia with Lewy bodies will be determined using the criteria of McKeith et a/. (2005). Neuropathologic diagnostic criteria for frontotemporal lobar degeneration will be determined using the consensus criteria of Cairns et a/. (2007). Other criteria will be applied where appropriate. 2. To perform brain autopsies and to collect, store at -80[unreadable]C, and distribute frozen and formalin fixed, paraffin wax-embedded tissues to support HASD projects and investigators and outside collaborations that complement in-house research. 3. To maintain a neuropathology computerized database in concert with the Biostatistics and Clinical Cores and the Washington University Neuroscience Blueprint Interdisciplinary Center Core (P30-NS057105). Information stored will include macroscopic images of fresh and fixed brain, demographic data, diagnoses, semi-quantitative morphometric data, neuropathology reports (in collaboration with Dr Schmidt, Chair, Division of Neuropathology), bibliographic information, and data relevant to Core tissue banking activities. In addition, neuropathology data will be transferred, after Biostatistics Core quality control and validation, to the National Alzheimer Coordinating Center (NACC), Washington University, Seattle, WA (U01-AG016976). 4. To establish Consensus Criteria for the Neuropathologic Diagnosis of Early AD. A major achievement of this project will be the establishment of new pathological diagnostic criteria for the earliest brain changes of AD. Using immunohistochemical and stereological methods the early changes associated with disease will be quantified and consensus criteria developed. Together, this project and the supporting cores will define the earliest pathological and biochemical stages of AD in comparison with healthy brain aging. To accomplish these aims, Core D will work closely with other Cores, Core leaders and Project leaders. There is no budgetary or scientific overlap with the activities of the Neuropathology Core and Brain Tissue Bank of the Washington University Alzheimer's Disease Research Center (ADRC).
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2010 — 2014 |
Cairns, Nigel John |
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 Core
The aims of the Neuropathology Core will be: 1. To make neuropathologic diagnoses on all new brain accessions from ADRC research subjects using standard diagnostic criteria where possible. The staging of Alzheimer's disease (AD) lesions will be assessed according to the protocols of Braak and Braak [9] and updated t o include an immunohistochemical assessment of lesions as proposed in 2006 [8]. Lewy body pathology will be rated according to the scheme proposed by Braak et al. [10] and McKeith et al. [28,27,26]. To ensure fidelity with the diagnostic criteria used for alI cases since 1985, we continue to use the neuropathologic diagnostic criteria of Khachaturian [22] for AD and also provide diagnoses in every case using criteria of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) [30] and the probabilistic criteria proposed by the National Institute on Aging and Reagan Institute [ 1]. ( See B. Background and Significance). 2. To perform brain autopsies and to collect, store at -80¿C, and distribute fixed and frozen brain tissue samples to support ADRC projects and investigators and outside research collaborations. 3. To maintain a computerized neuropathology database in concert with the Data Management and Statistics (Core C) and the Clinical Core (B) and the Washington University Center for Biomedical Informatics (CBMI). Information stored will include macroscopic images of fresh and fixed brain, demographic data, diagnoses, semi-quantitative morphometric data, neuropathology reports (in collaboration with Dr Schmidt, Chair. Division of Neuropathology), bibliographic information, and data relevant to Core tissue banking activities. In addition, neuropathology data will be transferred, after Core C quality control and validation, to the National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, WA (U01-AG016976). 4. To support Project 3 (role of APOE e3 and e4 proteins in AD) by providing tissue samples from 96 cases together with quantitative morphometric data including ABeta load and integrate with all aspects of the ADRC.
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2014 — 2018 |
Cairns, Nigel John |
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 D: Neuropathology
Core D: Neuropathology Project Summary/Abstract Although there have been significant advances in the identification of biomarkers of Alzheimer's disease (AD), comorbidity is a common finding at autopsy and the neuropathologic assessment at autopsy remains the gold standard for diagnosis. The aims of the Neuropathology Core (Core D) will be: (1) To make neuropathologic diagnoses on all new brain accessions from HASD research participants using standard diagnostic criteria; (2) To perform brain autopsies and to collect, store at -80?C, and distribute formalin-fixed, paraffin-embedded, and frozen brain tissue samples to support HASD Projects and investigators and outside collaborations that enhance HASD research goals; (3) To support Projects 1 and 2 by providing a neuropathologic assessment and quantitative measures of the molecular pathology (beta- amyloidosis, tauopathy, synucleinopathy, and TDP-43 proteinopathy) of cases which come to autopsy. To support the Specific Aims of Project 3 by providing neuropathologic data, quantitative measures of the molecular pathology, and tissue (for mRNA and DNA extraction) relating to cases recruited for the study of genetic variants and their influence on the progression of AD (4) To maintain a computerized neuropathology database (CaTissue) in concert with the Biostatistics Core (Core C) and the Clinical Core (Core B) and the Washington University Neuroscience Blueprint Interdisciplinary Center Core (P30 NS057105). Information stored will include macroscopic images of fresh and fixed brain, demographic data, diagnoses, semi- quantitative morphometric data, neuropathology reports in collaboration with Dr. Perrin, bibliographic information, and data relevant to Core tissue banking activities. If acceptable, neuropathology data also will be transferred, after Biostatistics Core quality control and validation, to the National Alzheimer Coordinating Center (NACC), University of Washington, Seattle, WA (U01 AG016976);(5) To undertake a developmental clinico-biomarker-neuropathologic study of HASD participants to determine the progression of biomarker changes in longitudinally assessed participants who transition from preclinical AD to symptomatic AD and who come to autopsy. Neuropathology will be the benchmark against which biomarker (CSF A?42 and pTau and PET-amyloid imaging) data will be assessed. With the Imaging and Biostatistics Cores and Projects 1 and 2, Core D will explore the contribution of AD biomarker changes with neuropathologic data including measures of A? and pTau burden, synaptic and neuronal loss.
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2014 |
Cairns, Nigel John |
UF1Activity Code Description: To support a discrete, specific, circumscribed project to be performed by the named investigator(s) in an area representing specific interest and competencies based on the mission of the agency, using standard peer review criteria. This is the multi-year funded equivalent of the U01 but can be used also for multi-year funding of other research project cooperative agreements such as UM1 as appropriate. |
Dian Neuropathology Core
The major goal of the Dominantly Inherited Alzheimer Network Neuropathology Core (DIAN-NPC) is to provide a neuropathological diagnosis on all participants in DIAN and family members who come to autopsy, to exchange data with the DIAN Coordinating Center, and to provide diagnostic reports and tissues to collaborating sites. The DIAN-NPC provides the
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2015 — 2018 |
Cairns, Nigel John |
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. |
Core D: Neuropathology Core
Core D: Neuropathology Project Summary/Abstract Neuropathology is essential to identify the true causes of brain disease. Although biomarkers are increasingly valuable as harbingers of disease in presymptomatic stages, there remains a need to validate CSF and neuroimaging biomarkers. In the older brain, more than one disease often is at work and at present only a detailed neuropathologic examination can determine the presence of coexisting diseases which may contribute in complex ways to the progression to dementia. Thus, the Neuropathology Core is essential for the ADRC to achieve its stated goals. Specifically, The Neuropathology Core has the following aims: Aim 1: To make neuropathologic diagnoses on all new brain accessions from ADRC research participants using standard diagnostic criteria. Aim 2: To perform brain autopsies and to collect, store, and distribute formalin-fixed, paraffin-embedded, and frozen brain tissue samples to support ADRC projects and investigators and outside collaborations that enhance ADRC research goals. Aim 3: To develop and maintain a computerized neuropathology database (CaTissue) in concert with the Data Management and Biostatistics Core (Core C) and the Clinical Core (Core B). Another interaction of the Neuropathology Core with the Clinical Core is to work closely with the Clinical Core autopsy coordinator, who is instrumental in arranging autopsy permission and in making arrangements for the body once death has occurred. This includes transporting the body to WUSM for autopsy. Aim 4: To support Project 2 (Aim 3), Core D will provide clinically and neuropathologically well-characterized cases of AD with and without Lewy bodies to determine how Aß and ?-synuclein compete for clearance pathways. Aim 5: To support Project 1 (Aim 2C) Core D will quantify the molecular pathology (tauopathy and ß-amyloidosis) in those participants who have undergone 18F-T807tau and 18F-florbetapir amyloid imaging who have come to autopsy in order to correlate PET amyloid and tau data with lesion number and density in histological sections of brain-matched areas.
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