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We investigated the off‐target binding of amyloid‐beta (Aβ) target [18F]florapronol ([18F]FC119S) using postmortem Alzheimer's disease (AD) brain tissue, compared with a known Aβ target imaging agent, [125I]TZDM and tau targeting [125I]MK as positive and negative controls, respectively. Off‐target binding of monoamine oxidase‐A and ‐B (MAO‐A and ‐B) was screened for FC119S and Pittsburgh compound B (PiB). Autoradiography (ARG) was performed to screen the Aβ‐binding potential using human AD postmortem brain tissue sections. Colocalization was quantitatively analyzed by using image analysis software. Pathological analysis was performed for screening of specific binding of amyloid‐beta and phospho‐tau. Amyloid‐beta targeting [18F]FC119S and [125I]TZDM tracers were showed a similar binding pattern in ARG, but [125I]MK was showed a different binding patterns. In the blocking experiment, [18F]FC119S binding was effectively blocked by a cold TZDM compound. FC119S and PiB were not showed specific binding with MAO‐A and MAO‐B. The autoradiographic binding pattern was positively correlated with the Aβ expression. [ABSTRACT FROM AUTHOR]

Recipients of hematopoietic stem cell transplantation (HSCT) are at significant risk for toxicity following the procedure. In these immunocompromised patients, infections frequently complicate the transplant course, adding to morbidity and mortality of this population. Therefore, clinicians often feel the need to screen patients for preexisting infections to reduce the risk of post-HSCT complications, for which computed tomography (CT) imaging of the sinuses, chest, and abdomen/pelvis is often performed. Although this imaging may detect an infection, it increases the patient's radiation exposure, and it may complicate the scheduling of the pre-HSCT evaluation. Also, potential imaging artifacts may lead to unnecessary medical evaluations or delays in HSCT. Moreover, patients with non-malignant disorders as indication for HSCT are not as likely to have significant infection risk prior to transplant, compared to those with malignant conditions who are more severely immunocompromised. After institutional review board approval, a retrospective study of patients who received HSCT at Children's Hospital of Pittsburgh from 2011 to 2017 was conducted. Of the 80 eligible patients, those who received chemotherapy prior to evaluation for HSCT, and patients who did not have CT scanning done as part of pre-HSCT evaluation were excluded. Thus, 55 subjects were included in this analysis. A univariate logistic analysis was performed to determine potential predictors of abnormal sinus, chest, abdomen/pelvis CT scans. Overall, 27 of 148 CT scans (18%) had positive findings. Of the 20 patients who had additional evaluation done based on these findings, 11 (55%) were related to chest CT findings, compared to 5 (25%) and 4 (20%) related to sinus and abdomen/pelvis CT, respectively. There were no variables that could predict positive findings on sinus and abdomen/pelvis CT scans. However, significant findings on chest CT scans were associated with certain predictors such as age (18 and older), graft type (peripheral blood) and pertinent infection history. The 5-year overall survival (OS) for patients with positive chest CT findings was 62.5%, in comparison to 91.5% for those with negative chest CT findings (P=0.049, OR=6.45). Our findings suggest that routine pre-HSCT CT screening in pediatric patients with non-malignant disorders rarely identifies abnormalities that lead to significant changes in clinical management. This study did not identify predictors for positive sinus and abdomen/pelvis CT scans. For chest CT, age, graft type and previous infection history were found to be predictors for abnormal findings. Moreover, patients with positive pre-HSCT CT scans were found to have lower survival rate, correlating to their higher prevalence of previous infection history. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta‐amyloid (Aβ) and tau deposition in older adults with a diverse cognitive spectrum. Methods: A total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [11C] Pittsburgh compound B and [18F] AV‐1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed. Results: Increased EPVS in the BG showed a significant association with lower cerebral tau deposition, even after controlling for other small vessel disease markers. Further exploratory analyses showed that this association was significant in cognitively impaired, Aβ‐positive, or APOE4‐positive individuals, but not significant in the cognitively normal, Aβ‐negative, or APOE4‐negative participants. In contrast to EPVS in the BG, EPVS in the CSO did not have any relationship with cerebral tau deposition. In addition, none of the two types of EPVS were associated with cerebral Aβ deposition. Conclusion: Brain tau deposition appears to be reduced with increased EPVS in the BG, especially in individuals with cognitive impairment, pathological amyloid burden, or genetic Alzheimer's disease risk. [ABSTRACT FROM AUTHOR]

Background: Hypertension has been associated with Alzheimer's disease (AD) dementia as well as vascular dementia. However, the underlying neuropathological changes that link hypertension to AD remain poorly understood. In our study, we examined the relationships of a history of hypertension and high current blood pressure (BP) with in vivo AD pathologies including β-amyloid (Aβ) and tau and also investigated whether a history of hypertension and current BP respectively affect the association between Aβ and tau deposition. Methods: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort study. Cognitively normal older adults who underwent both Aβ and tau positron emission tomography (PET) (i.e., [11C]-Pittsburgh compound B and [18F] AV-1451 PET) were selected. History of hypertension and current BP were evaluated and cerebral Aβ and tau deposition measured by PET were used as main outcomes. Generalized linear regression models were used to estimate associations. Results: A total of 68 cognitively normal older adults (mean [SD] age, 71.5 [7.4] years; 40 women [59%]) were included in the study. Neither a history of hypertension nor the current BP exhibited a direct association with Aβ or tau deposition. However, the synergistic interaction effects of high current systolic (β, 0.359; SE, 0.141; p = 0.014) and diastolic (β, 0.696; SE, 0.158; p < 0.001) BP state with Aβ deposition on tau deposition were significant, whereas there was no such effect for a history of hypertension (β, 0.186; SE, 0.152; p = 0.224). Conclusions: The findings suggest that high current BP, but not a history of hypertension, synergistically modulate the relationship between cerebral Aβ and tau deposition in late-life. In terms of AD prevention, the results support the importance of strict BP control in cognitively normal older adults with hypertension. [ABSTRACT FROM AUTHOR]

Background: Hypertension has been associated with Alzheimer's disease (AD) dementia as well as vascular dementia. However, the underlying neuropathological changes that link hypertension to AD remain poorly understood. In our study, we examined the relationships of a history of hypertension and high current blood pressure (BP) with in vivo AD pathologies including β-amyloid (Aβ) and tau and also investigated whether a history of hypertension and current BP respectively affect the association between Aβ and tau deposition. Methods: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort study. Cognitively normal older adults who underwent both Aβ and tau positron emission tomography (PET) (i.e., [11C]-Pittsburgh compound B and [18F] AV-1451 PET) were selected. History of hypertension and current BP were evaluated and cerebral Aβ and tau deposition measured by PET were used as main outcomes. Generalized linear regression models were used to estimate associations. Results: A total of 68 cognitively normal older adults (mean [SD] age, 71.5 [7.4] years; 40 women [59%]) were included in the study. Neither a history of hypertension nor the current BP exhibited a direct association with Aβ or tau deposition. However, the synergistic interaction effects of high current systolic (β, 0.359; SE, 0.141; p = 0.014) and diastolic (β, 0.696; SE, 0.158; p < 0.001) BP state with Aβ deposition on tau deposition were significant, whereas there was no such effect for a history of hypertension (β, 0.186; SE, 0.152; p = 0.224). Conclusions: The findings suggest that high current BP, but not a history of hypertension, synergistically modulate the relationship between cerebral Aβ and tau deposition in late-life. In terms of AD prevention, the results support the importance of strict BP control in cognitively normal older adults with hypertension. [ABSTRACT FROM AUTHOR]

Background: Despite the known associations between zinc levels and Alzheimer's disease (AD) dementia and related cognitive impairment, the underlying neuropathological links remain poorly understood. We tested the hypothesis that serum zinc level is associated with cerebral beta-amyloid protein (Aβ) deposition. Additionally, we explored associations between serum zinc levels and other AD pathologies [i.e., tau deposition and AD-signature cerebral glucose metabolism (AD-CM)] and white matter hyperintensities (WMHs), which are measures of cerebrovascular injury. Methods: A total of 241 cognitively normal older adults between 55 and 90 years of age were enrolled. All the participants underwent comprehensive clinical assessments, serum zinc level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Zinc levels were stratified into three categories: < 80 μg/dL (low), 80 to 90 μg/dL (medium), and > 90 μg/dL (high). Results: A low serum zinc level was significantly associated with increased Aβ retention. In addition, apolipoprotein E ε4 allele (APOE4) status moderated the association: the relationship between low zinc level and Aβ retention was significant only in APOE4 carriers. Although a low zinc level appeared to reduce AD-CM, the relationship became insignificant on sensitivity analysis including only individuals with no nutritional deficiency. The serum zinc level was associated with neither tau deposition nor the WMH volume. Conclusions: Our findings suggest that decreased serum zinc levels are associated with elevation of brain amyloid deposition. In terms of AD prevention, more attention needs to be paid to the role of zinc. [ABSTRACT FROM AUTHOR]