NEUROPATHOLOGY CORE

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The overall goal of the Neuropathology Core is to provide detailed morphologic, immunohistochemical, and biochemical evaluation of cerebrovascular disease, vascular brain injury, and neurodegeneration that may have contributed to cognitive impairment. This data will be provided to other Cores and projects in the program project grant (PPG), where they will be utilized in correlative studies. Specific aims are as follows: 1) To provide standardized pathologic assessment and accurate neuropathologic diagnoses for patients followed in the PPG, 2) To determine the relative contributions of ischemic vascular lesions and white matter alterations, AD pathologic changes, and Lewy bodies, to cognitive impairment and dementia in elderly patients. 3) To characterize, quantitatively and qualitatively, atherosclerosis, arteriosclerosis/arteriolosclerosis, and cerebral amyloid angiopathy. To correlate these abnormalities with severity of cervical carotid intima media thickening and retinal artery diameters measured in vivo. 4) To define morphologic parameters that may represent reliable biomarkers of brain injury which are a consequence of complete ischemia resulting in necrosis, downstream and upstream effects of this injury (e.g. Wallerian and trans-synaptic degeneration); to define morphologic correlates of 'sub-infarctive ischemia;' to assess cortical synaptic integrity within the cortex, as well as cell populations within the CMS (astrocytes, microglia) that may represent footprints of central nervous system injury. 5) To assess severity of Alzheimer disease changes in the brain, providing quantitative estimates of ABeta and tau pathologic lesions within brain parenchyma of autopsy patients. To distinguish oligomeric from ABeta deposition in the neocortex, allowing for comparisons with results from in vivo amyloid imaging with Pittsburgh imaging compound B (PIB). 6) To provide other Cores and Projects within the PPG quantitative neuropathologic and neurovascular data, allowing for correlations between antemortem neuropsychological and neuroimaging studies and autopsy neuropathologic findings.