Browsing by Author "Deters, Kacie D."

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    [(11)C]PiB PET in Gerstmann-Sträussler-Scheinker disease
    (e-Century Publishing Corporation, 2016) Deters, Kacie D.; Risacher, Shannon L.; Yoder, Karmen K.; Oblak, Adrian L.; Unverzagt, Frederick W.; Murrell, Jill R.; Epperson, Francine; Tallman, Eileen F.; Quaid, Kimberly A.; Farlow, Martin R.; Saykin, Andrew J.; Ghetti, Bernardino; Department of Pathology & Laboratory Medicine, IU School of Medicine
    Gerstmann-Sträussler-Scheinker Disease (GSS) is a familial neurodegenerative disorder characterized clinically by ataxia, parkinsonism, and dementia, and neuropathologically by deposition of diffuse and amyloid plaques composed of prion protein (PrP). The purpose of this study was to evaluate if [(11)C]Pittsburgh Compound B (PiB) positron emission tomography (PET) is capable of detecting PrP-amyloid in PRNP gene carriers. Six individuals at risk for GSS and eight controls underwent [(11)C]PiB PET scans using standard methods. Approximately one year after the initial scan, each of the three asymptomatic carriers (two with PRNP P102L mutation, one with PRNP F198S mutation) underwent a second [(11)C]PiB PET scan. Three P102L carriers, one F198S carrier, and one non-carrier of the F198S mutation were cognitively normal, while one F198S carrier was cognitively impaired during the course of this study. No [(11)C]PiB uptake was observed in any subject at baseline or at follow-up. Neuropathologic study of the symptomatic individual revealed PrP-immunopositive plaques and tau-immunopositive neurofibrillary tangles in cerebral cortex, subcortical nuclei, and brainstem. PrP deposits were also numerous in the cerebellar cortex. This is the first study to investigate the ability of [(11)C]PiB PET to bind to PrP-amyloid in GSS F198S subjects. This finding suggests that [(11)C]PiB PET is not suitable for in vivo assessment of PrP-amyloid plaques in patients with GSS.
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    Cerebral hypometabolism and grey matter density in MAPT intron 10 +3 mutation carriers
    (e-Century Publishing Corporation, 2014) Deters, Kacie D.; Risacher, Shannon L.; Farlow, Martin R.; Unverzagt, Frederick W.; Kareken, David A.; Hutchins, Gary D.; Yoder, Karmen K.; Murrell, Jill R.; Spina, Salvatore; Epperson, Francine; Gao, Sujuan; Saykin, Andrew J.; Ghetti, Bernardino; Department of Radiology and Imaging Sciences, IU School of Medicine
    Multiple systems tauopathy with presenile dementia (MSTD), a form of frontotemporal dementia with parkinsonism-17 with tau inclusions (FTDP-17T), is a neurodegenerative disorder caused by an (a) to (g) transition at position +3 of intron 10 of the microtubule associated protein tau (MAPT) gene. The mutation causes overexpression of 4 repeat (4R) tau isoforms with increased 4R/3R ratio leading to neurodegeneration. Clinically, these patients primarily present with behavioral variant FTD (bvFTD) and show disinhibition, disordered social comportment, and impaired executive function, memory, and speech. While altered glucose metabolism has been reported in subjects with sporadic bvFTD, it has yet to be investigated in an FTDP-17 sample of this size. In this study, eleven mutation carriers (5 males; mean age = 48.0 ± 6.9 years) and eight non-carriers (2 males; mean age = 43.7 ± 12.0 years) from a MSTD family were imaged using [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Eight of the MAPT intron 10 +3 mutation carriers met diagnostic criteria for bvFTD at the time of the PET scan, while three MAPT intron 10 +3 carriers were not cognitively impaired at the time of scan. Non-carriers had no clinically-relevant cognitive impairment at the time of the PET scan. Additionally, ten mutation carriers (5 males; mean age = 48.04 ± 2.1 years) and seven non-carriers (2 males; mean age 46.1 ± 4.1 years) underwent magnetic resonance imaging (MRI) which is an expanded sample size from a previous study. Seven MAPT mutation carriers met diagnostic criteria for bvFTD at the time of the MRI scan. Images were assessed on a voxel-wise basis for the effect of mutation carrier status. SPM8 was used for preprocessing and statistical analyses. Compared to non-carriers, MAPT mutation carriers showed lower [(18)F]FDG uptake bilaterally in the medial temporal lobe, and the parietal and frontal cortices. Anatomical changes were predominantly seen bilaterally in the medial temporal lobe areas which substantially overlapped with the hypometabolism findings. These anatomical and metabolic changes overlap previously described patterns of neurodegeneration in MSTD patients and are consistent with the characteristics of their cognitive dysfunction. These results suggest that neuroimaging can describe the neuropathology associated with this MAPT mutation.
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    Genome-wide association study of language performance in Alzheimer's disease
    (Elsevier, 2017-09) Deters, Kacie D.; Nho, Kwangsik; Risacher, Shannon L.; Kim, Sungeun; Ramanan, Vijay K.; Crane, Paul K.; Apostolova, Liana G.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas. GWAS identified GLI3 (GLI family zinc finger 3) as significantly associated with language performance (p<5×10-8). Enrichment of GWAS association was identified in pathways related to nervous system development and glutamate receptor function and trafficking. Our results, which warrant further investigation in independent and larger cohorts, implicate GLI3, a developmental transcription factor involved in patterning brain structures, as a putative gene associated with language dysfunction in AD.
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    Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease
    (IOS Press, 2017-06-23) Deters, Kacie D.; Risacher, Shannon L.; Kim, Sungeun; Nho, Kwangsik; West, John D.; Blennow, Kaj; Zetterberg, Henrik; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer’s disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study., Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis., Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ɛ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ+) if CSF Aβ42 was <192 pg/mL., Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ+ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus., Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ+ participants and not Aβ–participants.
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    Sex, racial, and APOE-ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer’s disease
    (bioRxiv, 2024-06-12) Peterson, Amalia; Sathe, Aditi; Zaras, Dimitrios; Yang, Yisu; Durant, Alaina; Deters, Kacie D.; Shashikumar, Niranjana; Pechman, Kimberly R.; Kim, Michael E.; Gao, Chenyu; Khairi, Nazirah Mohd; Li, Zhiyuan; Yao, Tianyuan; Huo, Yuankai; Dumitrescu, Logan; Gifford, Katherine A.; Wilson, Jo Ellen; Cambronero, Francis; Risacher, Shannon L.; Beason-Held, Lori L.; An, Yang; Arfanakis, Konstantinos; Erus, Guray; Davatzikos, Christos; Tosun, Duygu; Toga, Arthur W.; Thompson, Paul M.; Mormino, Elizabeth C.; Zhang, Panpan; Schilling, Kurt; Alzheimer’s Disease Neuroimaging Initiative (ADNI); BIOCARD Study Team; Alzheimer’s Disease Sequencing Project (ADSP); Albert, Marilyn; Kukull, Walter; Biber, Sarah A.; Landman, Bennett A.; Johnson, Sterling C.; Schneider, Julie; Barnes, Lisa L.; Bennett, David A.; Jefferson, Angela L.; Resnick, Susan M.; Saykin, Andrew J.; Hohman, Timothy J.; Archer, Derek B.; Radiology and Imaging Sciences, School of Medicine
    Introduction: The effects of sex, race, and Apolipoprotein E (APOE) - Alzheimer's disease (AD) risk factors - on white matter integrity are not well characterized. Methods: Diffusion MRI data from nine well-established longitudinal cohorts of aging were free-water (FW)-corrected and harmonized. This dataset included 4,702 participants (age=73.06 ± 9.75) with 9,671 imaging sessions over time. FW and FW-corrected fractional anisotropy (FAFWcorr) were used to assess differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. Results: Sex differences in FAFWcorr in association and projection tracts, racial differences in FAFWcorr in projection tracts, and APOE-ε4 differences in FW limbic and occipital transcallosal tracts were most pronounced. Discussion: There are prominent differences in white matter microstructure by sex, race, and APOE-ε4 carrier status. This work adds to our understanding of disparities in AD. Additional work to understand the etiology of these differences is warranted.