Browsing by Author "Price, Julie C."

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    11C-PiB PET can underestimate brain amyloid-β burden when cotton wool plaques are numerous
    (Oxford University Press, 2022) Abrahamson, Eric E.; Kofler, Julia K.; Becker, Carl R.; Price, Julie C.; Newell, Kathy L.; Ghetti, Bernardino; Murrell, Jill R.; McLean, Catriona A.; Lopez, Oscar L.; Mathis, Chester A.; Klunk, William E.; Villemagne, Victor L.; Ikonomovic, Milos D.; Pathology and Laboratory Medicine, School of Medicine
    Individuals with familial Alzheimer's disease due to PSEN1 mutations develop high cortical fibrillar amyloid-β load but often have lower cortical 11C-Pittsburgh compound B (PiB) retention than Individuals with sporadic Alzheimer's disease. We hypothesized this is influenced by limited interactions of Pittsburgh compound B with cotton wool plaques, an amyloid-β plaque type common in familial Alzheimer's disease but rare in sporadic Alzheimer's disease. Histological sections of frontal and temporal cortex, caudate nucleus and cerebellum were obtained from 14 cases with sporadic Alzheimer's disease, 12 cases with familial Alzheimer's disease due to PSEN1 mutations, two relatives of a PSEN1 mutation carrier but without genotype information and three non-Alzheimer's disease cases. Sections were processed immunohistochemically using amyloid-β-targeting antibodies and the fluorescent amyloid stains cyano-PiB and X-34. Plaque load was quantified by percentage area analysis. Frozen homogenates from the same brain regions from five sporadic Alzheimer's disease and three familial Alzheimer's disease cases were analysed for 3H-PiB in vitro binding and concentrations of amyloid-β1-40 and amyloid-β1-42. Nine sporadic Alzheimer's disease, three familial Alzheimer's disease and three non-Alzheimer's disease participants had 11C-PiB PET with standardized uptake value ratios calculated using the cerebellum as the reference region. Cotton wool plaques were present in the neocortex of all familial Alzheimer's disease cases and one sporadic Alzheimer's disease case, in the caudate nucleus from four familial Alzheimer's disease cases, but not in the cerebellum. Cotton wool plaques immunolabelled robustly with 4G8 and amyloid-β42 antibodies but weakly with amyloid-β40 and amyloid-βN3pE antibodies and had only background cyano-PiB fluorescence despite labelling with X-34. Relative to amyloid-β plaque load, cyano-Pittsburgh compound B plaque load was similar in sporadic Alzheimer's disease while in familial Alzheimer's disease it was lower in the neocortex and the caudate nucleus. In both regions, insoluble amyloid-β1-42 and amyloid-β1-40 concentrations were similar in familial Alzheimer's disease and sporadic Alzheimer's disease groups, while 3H-PiB binding was lower in the familial Alzheimer's disease than the sporadic Alzheimer's disease group. Higher amyloid-β1-42 concentration associated with higher 3H-PiB binding in sporadic Alzheimer's disease but not familial Alzheimer's disease. 11C-PiB retention correlated with region-matched post-mortem amyloid-β plaque load; however, familial Alzheimer's disease cases with abundant cotton wool plaques had lower 11C-PiB retention than sporadic Alzheimer's disease cases with similar amyloid-β plaque loads. PiB has limited ability to detect amyloid-β aggregates in cotton wool plaques and may underestimate total amyloid-β plaque burden in brain regions with abundant cotton wool plaques.
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    Comparison of amyloid accumulation between Down syndrome and autosomal-dominant Alzheimer disease
    (Wiley, 2022) Boerwinkle, Anna H.; Gordon, Brian A.; Wisch, Julie K.; Flores, Shaney; Henson, Rachel L.; Butt, Omar Hameed; Chen, Charles D.; Benzinger, Tammie L. S.; Fagan, Anne M.; Handen, Benjamin L.; Christian, Bradley T.; Head, Elizabeth; Mapstone, Mark; Klunk, William E.; Rafii, Michael S.; O’Bryant, Sid E.; Price, Julie C.; Schupf, Nicole; Laymon, Charles M.; Krinsky-McHale, Sharon J.; Lai, Florence; Rosas, H. Diana; Hartley, Sigan L.; Zaman, Shahid; Lott, Ira T.; Silverman, Wayne; Brickman, Adam M.; Lee, Joseph H.; Allegri, Ricardo Francisco; Berman, Sarah; Chhatwal, Jasmeer P.; Chui, Helena C.; Cruchaga, Carlos; Farlow, Martin R.; Fox, Nick C.; Goate, Alison; Day, Gregory S.; Graff-Radford, Neill R.; Jucker, Mathias; Lee, Jae-Hong; Levin, Johannes; Martins, Ralph N.; Mori, Hiroshi; Perrin, Richard J.; Salloway, Stephen P.; Sanchez-Valle, Raquel; Schofield, Peter R.; Xiong, Chengjie; Karch, Celeste M.; Hassenstab, Jason J.; McDade, Eric; Bateman, Randall J.; Ances, Beau M.; Neurology, School of Medicine
    Background: Given the triplication of chromosome 21 and the location of the amyloid precursor protein gene on chromosome 21, almost all adults with Down syndrome (DS) develop Alzheimer disease (AD)-like pathology and dementia during their lifetime. Comparing amyloid accumulation in DS to autosomal dominant AD (ADAD), another genetic form of AD, may improve our understanding of early AD pathology development. Method: We assessed amyloid positron emission tomography (PET) imaging in 192 participants with DS and 33 sibling controls from the Alzheimer’s Biomarker Consortium-Down Syndrome (ABC-DS) and 265 mutation-carriers (MC) and 169 familial controls from the Dominantly Inherited Alzheimer Network (DIAN) (Table 1). We calculated regional standard uptake value ratios (SUVR) using a cerebellar cortex reference region and converted global amyloid burden SUVR to centiloids. We compared amyloid PET by cognitive status and estimated-years-to-symptom-onset (EYO). EYO was calculated for DIAN participants by subtracting their age from parental age of symptom onset and for ABC-DS participants by subtracting their age from 50.2 years, a published average age of symptom onset in a large sample of individuals with DS (Fortea et al., 2020). In a subset of participants, we assessed the relationship between amyloid PET and CSF Aβ42/40. Result: The relationship between CSF Aβ42/40 and amyloid PET was similar in DS and MC participants (Figure 1). We did not observe significant differences between MC and DS grouped by cognitive status (Figure 2). However, when assessed over EYO, global amyloid burden was significantly elevated in MC at EYO ≥ -23 but was not elevated in DS until EYO ≥ -15 (Figure 3). We observed early cortical and subcortical amyloid PET increases in both groups, but we also measured some regional differences in amyloid PET changes between MC and DS, specifically in the medial occipital region (Figure 4 and 5). Conclusion: These results demonstrate similarities in the relationship between amyloid biomarkers and the levels of amyloid accumulation in ADAD and DS. However, we also observed a 5-10 year delay and some regional differences in amyloid accumulation in DS. This is important for future clinical trials to consider when recruiting participants and determining treatment efficacy.
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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.