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Item Blood Selenium and Serum Glutathione Peroxidase Levels Were Associated with Serum β‑Amyloid in Older Adults(Springer, 2023) Luo, Jiao; Su, Liqin; He, Xiaohong; Du, Yegang; Xu, Ning; Wu, Rangpeng; Zhu, Yunfeng; Wang, Ting; Shao, Ranqi; Unverzagt, Frederick W.; Hake, Ann M.; Jin, Yinlong; Gao, Sujuan; Psychiatry, School of MedicineBackground: Studies have established the association between blood β-amyloid (Aβ) levels and Alzheimer's disease, but population-based studies concerning the association between selenium (Se) and Aβ levels in blood samples are very limited. Therefore, we explored the association in an elderly population with Se status and serum Aβ measures. Methods: A cross-sectional study on 469 elderly individuals from four rural counties with diverse soil Se levels was carried out. Fasting blood Se, serum selenoprotein P (SELENOP), and glutathione peroxidase (GPX), serum Aβ42, and Aβ40 were measured. Quantile regression models were used to determine the associations of blood Se, serum GPX, and SELENOP with Aβ levels. Results: Significant negative associations were observed between blood Se and serum Aβ42 and Aβ40 levels at all percentiles (P < 0.05). The associations were generally stronger at higher Aβ42 and Aβ40 percentiles than lower Aβ42 and Aβ40 percentiles. Blood Se was positively associated with serum Aβ42/Aβ40 ratio at 25th, 50th, and 75th percentiles. Significant positive associations were observed between serum GPX and Aβ42 and Aβ40 levels at all percentiles (P < 0.05). The positive associations were generally stronger at higher Aβ42 and Aβ40 percentiles than at lower percentiles. Serum GPX was negatively associated with Aβ42/Aβ40 ratio at 25th, 50th, 75th, and 95th percentiles. No associations with serum SELENOP and Aβ levels were observed. Conclusions: Our results suggest that higher Se levels are associated with lower serum Aβ42 and Aβ40 levels and with higher Aβ42/Aβ40 ratio, and the results are specific for different selenoproteins.Item Cdk5 activity in the brain - multiple paths of regulation(The Company of Biologists, 2014-06-01) Shah, Kavita; Lahiri, Debomoy; Department of Medical and Molecular Genetics, IU School of MedicineCyclin dependent kinase-5 (Cdk5), a family member of the cyclin-dependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5. © 2014. Published by The Company of Biologists Ltd.Item Contribution of clinical information to the predictive performance of plasma β-amyloid levels for amyloid positron emission tomography positivity(Frontiers Media, 2023-03-14) Chun, Min Young; Jang, Hyemin; Kim, Hee Jin; Kim, Jun Pyo; Gallacher, John; Allué, José Antonio; Sarasa, Leticia; Castillo, Sergio; Pascual-Lucas, María; Na, Duk L.; Seo, Sang Won; DPUK; Radiology and Imaging Sciences, School of MedicineBackground: Early detection of β-amyloid (Aβ) accumulation, a major biomarker for Alzheimer's disease (AD), has become important. As fluid biomarkers, the accuracy of cerebrospinal fluid (CSF) Aβ for predicting Aβ deposition on positron emission tomography (PET) has been extensively studied, and the development of plasma Aβ is beginning to receive increased attention recently. In the present study, we aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of plasma Aβ and CSF Aβ levels for Aβ PET positivity. Methods: We recruited 488 participants who underwent both plasma Aβ and Aβ PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) Aβ and Aβ PET studies (Cohort 2). Plasma and CSF samples were analyzed using ABtest-MS, an antibody-free liquid chromatography-differential mobility spectrometry-triple quadrupole mass spectrometry method and INNOTEST enzyme-linked immunosorbent assay kits, respectively. To evaluate the predictive performance of plasma Aβ and CSF Aβ, respectively, logistic regression and receiver operating characteristic analyses were performed. Results: When predicting Aβ PET status, both plasma Aβ42/40 ratio and CSF Aβ42 showed high accuracy (plasma Aβ area under the curve (AUC) 0.814; CSF Aβ AUC 0.848). In the plasma Aβ models, the AUC values were higher than plasma Aβ alone model, when the models were combined with either cognitive stage (p < 0.001) or APOE genotype (p = 0.011). On the other hand, there was no difference between the CSF Aβ models, when these variables were added. Conclusion: Plasma Aβ might be a useful predictor of Aβ deposition on PET status as much as CSF Aβ, particularly when considered with clinical information such as APOE genotype and cognitive stage.