The goals of the Neuropathology Core (NPC) will be to provide standardize neuropathologic assessment of brains obtained at autopsy from study patients who have been followed clinically, using neuropsychological evaluations and neuroimaging, in order to characterize the relative contributions of ischemic vascular lesions and parenchymal degenerative changes (e.g. of Alzheimer disease) to a given patient's dementia. Comparisons of specific neuropathologic parameters (see below) will be made among ischemic vascular dementia (IVD), Alzheimer and control patients. We will operationalize assessment of neuropathologic substrates of IVD by evaluating both (a) extent, and (b) distribution of encephalomalacic lesions that may contribute to dementia. A neuropathologic data base will be maintained and data will be provided to other projects as necessary to facilitate correlations between pre- mortem (including metabolic) imaging studies and postmortem brain findings, with an emphasis on defining radiographic features on lacunar infarcts, and their possible impact upon cortical integrity by mechanisms of retrograde and trans-synaptic degeneration. Possible neuroanatomical correlates of ischemic vascular dementia )IVD) to be evaluated in detail will include changes within white matter (axons, myelin sheaths) and densities and sizes of neurons projecting into the white matter (in conjugation with Project #3). Possible neuropathologic substrates of IVD to be evaluated, using immunohistochemistry and quantitative morphometry, will include (a) microvascular lesions characterized as abnormal distributions/densities of glucose transporter-immunoreactive capillaries, and hypertrophic arterioles, (b) secondary injurious effects of microvasculopathy upon adjacent brain parenchyma (e.g. axon/myeline densities of glucose transporter-immunoreactive capillaries, and hypertrophic arterioles, (b) secondary injurious effects of microvasculopathy upon adjacent brain parenchyma (e.g. axon/myelin densities , APP expression) and inflammatory/reactive cells (microglia, astrocytes), and (c) hippocampal abnormalities indicative of hippocampal sclerosis or scarring. Neuropathologic data will be provided to the investigational projects and all clinical/experimental data will be re- evaluated in these projects in light of neuropathologic outcomes. The intended result is to provide the most detailed available pathophysiologic representation of IVD based upon multi-modality functional and neuroanatomical patient evaluation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG012435-07
Application #
6472260
Study Section
Project Start
2001-07-15
Project End
2002-05-31
Budget Start
Budget End
Support Year
7
Fiscal Year
2001
Total Cost
$268,421
Indirect Cost
Name
University of Southern California
Department
Type
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Haaksma, Miriam L; Calderón-Larrañaga, Amaia; Olde Rikkert, Marcel G M et al. (2018) Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes. Int J Geriatr Psychiatry 33:1057-1064
La Joie, Renaud; Ayakta, Nagehan; Seeley, William W et al. (2018) Multisite study of the relationships between antemortem [11C]PIB-PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology. Alzheimers Dement :
Lao, Yi; Nguyen, Binh; Tsao, Sinchai et al. (2017) A T1 and DTI fused 3D corpus callosum analysis in MCI subjects with high and low cardiovascular risk profile. Neuroimage Clin 14:298-307
Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce et al. (2017) Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort. Dement Geriatr Cogn Disord 44:1-11
Seo, Sang Won; Ayakta, Nagehan; Grinberg, Lea T et al. (2017) Regional correlations between [11C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort. Neuroimage Clin 13:130-137
Zheng, Ling; Vinters, Harry V; Mack, Wendy J et al. (2016) Differential effects of ischemic vascular disease and Alzheimer's disease on brain atrophy and cognition. J Cereb Blood Flow Metab 36:204-15
Durazzo, Timothy C; Korecka, Magdalena; Trojanowski, John Q et al. (2016) Active Cigarette Smoking in Cognitively-Normal Elders and Probable Alzheimer's Disease is Associated with Elevated Cerebrospinal Fluid Oxidative Stress Biomarkers. J Alzheimers Dis 54:99-107
Villeneuve, Sylvia; Rabinovici, Gil D; Cohn-Sheehy, Brendan I et al. (2015) Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation. Brain 138:2020-33
Bron, Esther E; Smits, Marion; van der Flier, Wiesje M et al. (2015) Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: the CADDementia challenge. Neuroimage 111:562-79
Vinters, Harry V (2015) Emerging concepts in Alzheimer's disease. Annu Rev Pathol 10:291-319

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