Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease

Tammie L S Benzinger, Tyler Blazey, Clifford R Jr. Jack, Robert A. Koeppe, Yi Su, Chengjie Xiong, Marcus E. Raichle, Abraham Z. Snyder, Beau M. Ances, Randall J. Bateman, Nigel J. Cairns, Anne M. Fagan, A. Goate, Daniel S. Marcus, Paul S. Aisen, Jon J. Christensen, Lindsay Ercole, Russ C. Hornbeck, Angela M. Farrar, Patricia AldeaMateusz S. Jasielec, Christopher J. Owen, Xianyun Xie, Richard Mayeux, Adam Brickman, Eric McDade, William Klunk, Chester A. Mathis, J. Ringman, Paul M. Thompson, Bernardino Ghetti, Andrew J. Saykin, Reisa A. Sperling, Keith A. Johnson, Stephen Salloway, Stephen Correia, Peter R. Schofield, Colin L. Masters, Christopher Rowe, Victor L. Villemagne, Ralph Martins, Sebastien Ourselin, Martin N. Rossor, Nick C. Fox, David M. Cash, Michael W. Weiner, David M. Holtzman, Virginia D. Buckles, Krista Moulder, John C. Morris

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Abstract

Major imaging biomarkers of Alzheimer's disease include amyloid deposition [imaged with [11C]Pittsburgh compound B (PiB) PET], altered glucose metabolism (imaged with [18F]fluro-deoxyglucose PET), and structural atrophy (imaged by MRI). Recently we published the initial subset of imaging findings for specific regions in a cohort of individuals with autosomal dominant Alzheimer's disease. We now extend this work to include a larger cohort, wholebrain analyses integrating all three imaging modalities, and longitudinal data to examine regional differences in imaging biomarker dynamics. The anatomical distribution of imaging biomarkers is described in relation to estimated years from symptom onset. Autosomal dominant Alzheimer's disease mutation carrier individuals have elevated PiB levels in nearly every cortical region 15 y before the estimated age of onset. Reduced cortical glucose metabolism and cortical thinning in the medial and lateral parietal lobe appeared 10 and 5 y, respectively, before estimated age of onset. Importantly, however, a divergent pattern was observed subcortically. All subcortical gray-matter regions exhibited elevated PiB uptake, but despite this, only the hippocampus showed reduced glucose metabolism. Similarly, atrophy was not observed in the caudate and pallidum despite marked amyloid accumulation. Finally, before hypometabolism, a hypermetabolic phase was identified for some cortical regions, including the precuneus and posterior cingulate. Additional analyses of individuals in which longitudinal data were available suggested that an accelerated appearance of volumetric declines approximately coincides with the onset of the symptomatic phase of the disease.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number47
DOIs
StatePublished - Nov 19 2013

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Benzinger, T. L. S., Blazey, T., Jack, C. R. J., Koeppe, R. A., Su, Y., Xiong, C., Raichle, M. E., Snyder, A. Z., Ances, B. M., Bateman, R. J., Cairns, N. J., Fagan, A. M., Goate, A., Marcus, D. S., Aisen, P. S., Christensen, J. J., Ercole, L., Hornbeck, R. C., Farrar, A. M., ... Morris, J. C. (2013). Regional variability of imaging biomarkers in autosomal dominant Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 110(47). https://doi.org/10.1073/pnas.1317918110