Browsing by Author "Klunk, William"

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    Partial Volume Correction in Quantitative Amyloid Imaging.
    (Elsevier, 2015-02-15) Su, Yi; Blazey, Tyler M.; Snyder, Abraham Z.; Raichle, Marcus E.; Marcus, Daniel S.; Ances, Beau M.; Bateman, Randall J.; Cairns, Nigel J.; Aldea, Patricia; Cash, Lisa; Christensen, Jon J.; Friedrichsen, Karl; Hornbeck, Russ C.; Farrar, Angela M.; Owen, Christopher J.; Mayeux, Richard; Brickman, Adam M.; Klunk, William; Price, Julie C.; Thompson, Paul M.; Ghetti, Bernardino; Saykin, Andrew J.; Sperling, Reisa A.; Johnson, Keith A.; Schofield, Peter R.; Buckles, Virginia; Morris, John C.; Benzinger, Tammie LS; Department of Pathology & Laboratory Medicine, IU School of Medicine
    Amyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition.
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    Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome
    (IOS Press, 2021) Petersen, Melissa E.; Rafii, Michael S.; Zhang, Fan; Hall, James; Julovich, David; Ances, Beau M.; Schupf, Nicole; Krinsky-McHale, Sharon J.; Mapstone, Mark; Silverman, Wayne; Lott, Ira; Klunk, William; Head, Elizabeth; Christian, Brad; Foroud, Tatiana; Lai, Florence; Rosas, H. Diana; Zaman, Shahid; Wang, Mei-Cheng; Tycko, Benjamin; Lee, Joseph H.; Handen, Benjamin; Hartley, Sigan; Fortea, Juan; O’Bryant, Sid; Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS); Medical and Molecular Genetics, School of Medicine
    Background: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population. Objective: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults. Methods: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome. Results: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS. Conclusion: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.
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    Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease
    (Nature Research, 2019-02) Preische, Oliver; Schultz, Stephanie A.; Apel, Anja; Kuhle, Jens; Kaeser, Stephan A.; Barro, Christian; Gräber, Susanne; Kuder-Buletta, Elke; LaFougere, Christian; Laske, Christoph; Vöglein, Jonathan; Levin, Johannes; Masters, Colin L.; Martins, Ralph; Schofield, Peter R.; Rossor, Martin N.; Graff-Radford, Neill R.; Salloway, Stephen; Ghetti, Bernardino; Ringman, John M.; Noble, James M.; Chhatwal, Jasmeer; Goate, Alison M.; Benzinger, Tammie L. S.; Morris, John C.; Bateman, Randall J.; Wang, Guoqiao; Fagan, Anne M.; McDade, Eric M.; Gordon, Brian A.; Jucker, Mathias; Alzheimer Network; Allegri, Ricardo; Amtashar, Fatima; Bateman, Randall; Benzinger, Tammie; Berman, Sarah; Bodge, Courtney; Brandon, Susan; Brooks, William; Buck, Jill; Buckles, Virginia; Chea, Sochenda; Chhatwal, Jasmeer; Chrem, Patricio; Chui, Helena; Cinco, Jake; Clifford, Jack; Cruchaga, Carlos; D’Mello, Mirelle; Donahue, Tamara; Douglas, Jane; Edigo, Noelia; Erekin-Taner, Nilufer; Fagan, Anne; Farlow, Marty; Farrar, Angela; Feldman, Howard; Flynn, Gigi; Fox, Nick; Franklin, Erin; Fujii, Hisako; Gant, Cortaiga; Gardener, Samantha; Ghetti, Bernardino; Goate, Alison; Goldman, Jill; Gordon, Brian; Graff-Radford, Neill; Gray, Julia; Gurney, Jenny; Hassenstab, Jason; Hirohara, Mie; Holtzman, David; Hornbeck, Russ; DiBari, Siri Houeland; Ikeuchi, Takeshi; Ikonomovic, Snezana; Jerome, Gina; Jucker, Mathias; Karch, Celeste; Kasuga, Kensaku; Kawarabayashi, Takeshi; Klunk, William; Koeppe, Robert; Kuder-Buletta, Elke; Laske, Christoph; Lee, Jae-Hong; Levin, Johannes; Marcus, Daniel; Martins, Ralph; Mason, Neal Scott; Masters, Colin; Maue-Dreyfus, Denise; McDade, Eric; Montoya, Lucy; Mori, Hiroshi; Morris, John; Nagamatsu, Akem; Neimeyer, Katie; Noble, James; Norton, Joanne; Perrin, Richard; Raichle, Marc; Ringman, John; Roh, Jee Hoon; Salloway, Stephen; Schofield, Peter; Shimada, Hiroyuki; Shiroto, Tomoyo; Shoji, Mikio; Sigurdson, Wendy; Sohrabi, Hamid; Sparks, Paige; Suzuki, Kazushi; Swisher, Laura; Taddei, Kevin; Wang, Jen; Wang, Peter; Weiner, Mike; Wolfsberger, Mary; Xiong, Chengjie; Xu, Xiong; Pathology and Laboratory Medicine, School of Medicine
    Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker.
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    Utility of perfusion PET measures to assess neuronal injury in Alzheimer's disease
    (Elsevier, 2018-09-27) Joseph-Mathurin, Nelly; Su, Yi; Blazey, Tyler M.; Jasielec, Mateusz; Vlassenko, Andrei; Friedrichsen, Karl; Gordon, Brian A.; Hornbeck, Russ C.; Cash, Lisa; Ances, Beau M.; Veale, Thomas; Cash, David M.; Brickman, Adam M.; Buckles, Virginia; Cairns, Nigel J.; Cruchaga, Carlos; Goate, Alison; Jack, Clifford R., Jr.; Karch, Celeste; Klunk, William; Koeppe, Robert A.; Marcus, Daniel S.; Mayeux, Richard; McDade, Eric; Noble, James M.; Ringman, John; Saykin, Andrew J.; Thompson, Paul M.; Xiong, Chengjie; Morris, John C.; Bateman, Randall J.; Benzinger, Tammie L. S.; Dominantly Inherited Alzheimer Network; Radiology and Imaging Sciences, School of Medicine
    Introduction: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used to estimate neuronal injury in Alzheimer's disease (AD). Here, we evaluate the utility of dynamic PET measures of perfusion using 11C-Pittsburgh compound B (PiB) to estimate neuronal injury in comparison to FDG PET. Methods: FDG, early frames of PiB images, and relative PiB delivery rate constants (PiB-R1) were obtained from 110 participants from the Dominantly Inherited Alzheimer Network. Voxelwise, regional cross-sectional, and longitudinal analyses were done to evaluate the correlation between images and estimate the relationship of the imaging biomarkers with estimated time to disease progression based on family history. Results: Metabolism and perfusion images were spatially correlated. Regional PiB-R1 values and FDG, but not early frames of PiB images, significantly decreased in the mutation carriers with estimated year to onset and with increasing dementia severity. Discussion: Hypometabolism estimated by PiB-R1 may provide a measure of brain perfusion without increasing radiation exposure.