Browsing by Author "Sohn, Dongwha"

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    Characterizing Gene and Protein Crosstalks in Subjects at Risk of Developing Alzheimer’s Disease: A New Computational Approach
    (MDPI, 2017-08-17) Padmanabhan, Kanchana; Nudelman, Kelly; Harenberg, Steve; Bello, Gonzalo; Sohn, Dongwha; Shpanskaya, Katie; Tiwari Dikshit, Priyanka; Yerramsetty, Pallavi S.; Tanzi, Rudolph E.; Saykin, Andrew J.; Petrella, Jeffrey R.; Doraiswamy, P. Murali; Samatova, Nagiza F.; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Alzheimer’s disease (AD) is a major public health threat; however, despite decades of research, the disease mechanisms are not completely understood, and there is a significant dearth of predictive biomarkers. The availability of systems biology approaches has opened new avenues for understanding disease mechanisms at a pathway level. However, to the best of our knowledge, no prior study has characterized the nature of pathway crosstalks in AD, or examined their utility as biomarkers for diagnosis or prognosis. In this paper, we build the first computational crosstalk model of AD incorporating genetics, antecedent knowledge, and biomarkers from a national study to create a generic pathway crosstalk reference map and to characterize the nature of genetic and protein pathway crosstalks in mild cognitive impairment (MCI) subjects. We perform initial studies of the utility of incorporating these crosstalks as biomarkers for assessing the risk of MCI progression to AD dementia. Our analysis identified Single Nucleotide Polymorphism-enriched pathways representing six of the seven Kyoto Encyclopedia of Genes and Genomes pathway categories. Integrating pathway crosstalks as a predictor improved the accuracy by 11.7% compared to standard clinical parameters and apolipoprotein E ε4 status alone. Our findings highlight the importance of moving beyond discrete biomarkers to studying interactions among complex biological pathways.
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    Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer's disease
    (Nature Publishing Group, 2018-05-10) Sohn, Dongwha; Shpanskaya, Katie; Lucas, Joseph E.; Petrella, Jeffrey R.; Saykin, Andrew J.; Tanzi, Rudolph E.; Samatova, Nagiza F.; Doraiswamy, P. Murali; Radiology and Imaging Sciences, School of Medicine
    Sex differences in Alzheimer's disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer's and followed up to 10 years in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having "high" or "low" likelihood for MCI due to Alzheimer's. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer's Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer's was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer's disease progression.