The figure shows Pittsburgh Compound-B (PiB) positron emission tomography (PET) images from a cognitively normal control, an Alzheimer's disease (AD) patient and a Mild Cognitive Impairment (MCI) patient. The images are not shown in the order listed and are intentionally not labeled to make the point that the presence, amount and regional distribution of fibrillar amyloid-beta (A?) deposits in the brain do not always correlate with cognitive function. Postmortem studies have shown this previously, but in vivo amyloid imaging allows us to explore this phenomenon in ways that were not previously possible. Two opposing conclusions can be drawn from this figure: 1) either fibrillar A? deposition is not related to the cognitive dysfunction of AD or 2) there are modulators of the effects of fibrillar A? deposition on cognition. To fully understand the pathophysiology of AD, we must address the question: """"""""Which factors determine the impact of A? deposition in a given individual?"""""""" Two of the most important diseases in the aging brain are AD and vascular disease. Many studies have shown that vascular disease can contribute to MCI and dementia. This Program Project renewal application proposes to take an integrative view on the inter-relationships between these two disorders and to examine how vascular disease may influence the presence and rate of progression of symptoms in individuals who have AD pathology in their brain. Finding the answer to this important question requires a combination of postmortem studies with in vivo studies to measure A? and its potential modulators in close temporal proximity to cognitive testing. We have a unique opportunity to perform postmortem analyses of subjects who underwent PiB-PET imaging and detailed clinical evaluation before death. The overall specific aims of this Program Project are to: 1) Determine whether a combination of A? and vascular """"""""Modulating Variables"""""""" (both systemic and cerebrovascular) improves the prediction of the Study Outcomes (i.e., cognition, brain metabolism and atrophy) over A? measures alone;and 2) Increase our understanding of the neuropathological substrates of PiB retention and the threshold for in vivo detection of A? deposition.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1)
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Hsiao, John
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University of Pittsburgh
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Mizukami, Katsuyoshi; Akatsu, Hiroyasu; Abrahamson, Eric E et al. (2016) Immunohistochemical analysis of hippocampal butyrylcholinesterase: Implications for regional vulnerability in Alzheimer's disease. Neuropathology 36:135-45
Ikonomovic, Milos D; Abrahamson, Eric E; Price, Julie C et al. (2016) [F-18]AV-1451 positron emission tomography retention in choroid plexus: More than ""off-target"" binding. Ann Neurol 80:307-8
Perez, Sylvia E; He, Bin; Nadeem, Muhammad et al. (2015) Resilience of precuneus neurotrophic signaling pathways despite amyloid pathology in prodromal Alzheimer's disease. Biol Psychiatry 77:693-703
Klunk, William E; Koeppe, Robert A; Price, Julie C et al. (2015) The Centiloid Project: standardizing quantitative amyloid plaque estimation by PET. Alzheimers Dement 11:1-15.e1-4
Marquié, Marta; Normandin, Marc D; Vanderburg, Charles R et al. (2015) Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol 78:787-800
Nichols, Noah; Bras, Jose M; Hernandez, Dena G et al. (2015) EIF4G1 mutations do not cause Parkinson's disease. Neurobiol Aging 36:2444.e1-4
Goodheart, A E; Tamburo, E; Minhas, D et al. (2015) Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities. Neuroimage Clin 9:479-83
Yau, Wai-Ying Wendy; Tudorascu, Dana L; McDade, Eric M et al. (2015) Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer's disease: a prospective cohort study. Lancet Neurol 14:804-13
Chen, Yin J; Rosario, Bedda L; Mowrey, Wenzhu et al. (2015) Relative 11C-PiB Delivery as a Proxy of Relative CBF: Quantitative Evaluation Using Single-Session 15O-Water and 11C-PiB PET. J Nucl Med 56:1199-205
Mountz, James M; Laymon, Charles M; Cohen, Ann D et al. (2015) Comparison of qualitative and quantitative imaging characteristics of [11C]PiB and [18F]flutemetamol in normal control and Alzheimer's subjects. Neuroimage Clin 9:592-8

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