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Background: Plasma neurofilament light chain (NfL) is a blood biomarker of neurodegeneration, including Alzheimer's disease. However, its usefulness may be influenced by common conditions in older adults, including amyloid-β (Aβ) deposition and cardiometabolic risk factors like hypertension, diabetes mellitus (DM), impaired kidney function, and obesity. This longitudinal observational study using the Alzheimer's Disease Neuroimaging Initiative cohort investigated how these conditions influence the prognostic capacity of plasma NfL. Methods: Non-demented participants (cognitively unimpaired or mild cognitive impairment) underwent repeated assessments including the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores, hippocampal volumes, and white matter hyperintensity (WMH) volumes at 6- or 12-month intervals. Linear mixed-effect models were employed to examine the interaction between plasma NfL and various variables of interest, such as Aβ (evaluated using Florbetapir positron emission tomography), hypertension, DM, impaired kidney function, or obesity. Results: Over a mean follow-up period of 62.5 months, participants with a mean age of 72.1 years (n = 720, 48.8% female) at baseline were observed. Higher plasma NfL levels at baseline were associated with steeper increases in ADAS-Cog scores and WMH volumes, and steeper decreases in hippocampal volumes over time (all p-values < 0.001). Notably, Aβ at baseline significantly enhanced the association between plasma NfL and longitudinal changes in ADAS-Cog scores (p-value 0.005) and hippocampal volumes (p-value 0.004). Regarding ADAS-Cog score and WMH volume, the impact of Aβ was more prominent in cognitively unimpaired than in mild cognitive impairment. Hypertension significantly heightened the association between plasma NfL and longitudinal changes in ADAS-Cog scores, hippocampal volumes, and WMH volumes (all p-values < 0.001). DM influenced the association between plasma NfL and changes in ADAS-Cog scores (p-value < 0.001) without affecting hippocampal and WMH volumes. Impaired kidney function did not significantly alter the association between plasma NfL and longitudinal changes in any outcome variables. Obesity heightened the association between plasma NfL and changes in hippocampal volumes only (p-value 0.026). Conclusion: This study suggests that the prognostic capacity of plasma NfL may be amplified in individuals with Aβ or hypertension. This finding emphasizes the importance of considering these factors in the NfL-based prognostic model for neurodegeneration in non-demented older adults. [ABSTRACT FROM AUTHOR]

Aim: The neurobiological substrates underlying the relationship of circadian rest‐activity rhythm (RAR) alteration with accelerated late‐life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer disease (AD) pathologies and cerebrovascular injury was investigated in older adults without dementia. Methods: The present study included 129 participants without dementia who participated in the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease) cohort. All participants underwent actigraphy at baseline and two consecutive [11C] Pittsburgh compound‐B positron emission tomography (PET), [18F] fluorodeoxyglucose‐PET, magnetic resonance imaging, and Mini‐Mental State Examination (MMSE) at baseline and at a 2‐year follow‐up assessment. The associations of circadian RAR with annualized change in neuroimaging measures including global amyloid‐beta retention, AD‐signature region cerebral glucose metabolism (AD‐CM), and white matter hyperintensity volume were examined. Results: Delayed acrophase at baseline was significantly associated with greater annualized decline of AD‐CM over a 2‐year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD‐CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD‐CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score. Conclusion: The findings indicate that delayed acrophase in late life may cause or predict hypometabolism at AD‐signature brain regions, which underlies cognitive decline in the near future. [ABSTRACT FROM AUTHOR]

Background: Physical activities (PA) have been suggested to reduce the risk of Alzheimer's disease (AD) dementia. However, information on the neuropathological links underlying the relationship is limited.Objective: We investigated the role of midlife and late-life PA with in vivo AD neuropathologies in old adults without dementia.Methods: This study included participants from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (KBASE). The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] fluorodeoxyglucose PET, and magnetic resonance imaging. Using the multi-modal brain imaging data, in vivo AD pathologies including global amyloid deposition, AD-signature region cerebral glucose metabolism (AD-CM), and AD-signature region cortical thickness (AD-CT) were quantified. Both midlife and late-life PA of participants were measured using the Lifetime Total Physical Activity Questionnaire.Results: This study was performed on 260 participants without dementia (195 with normal cognitive function and 65 with mild cognitive impairment). PA of neither midlife nor late-life showed direct correspondence with any neuroimaging biomarker. However, late-life PA moderated the relationship of brain amyloid-β (Aβ) deposition with AD-CM and AD-CT. Aβ positivity had a significant negative effect on both AD-CM and AD-CT in individuals with lower late-life PA, but those with higher late-life PA did not show such results. Midlife PA did not have such a moderation effect.Conclusion: The findings suggest that physically active lifestyle in late-life, rather than that in midlife, may delay AD-associated cognitive decline by decreasing Aβ-induced neurodegenerative changes in old adults. [ABSTRACT FROM AUTHOR]

89Zr is an emerging radionuclide with promising application in nuclear medicine for the non-invasive diagnosis of various cancers with PET imaging. This paper would discuss optimization efforts in the production of 89Zr carried out at Accelerator Radioisotope Development Team, Korea Atomic Energy Research Institute. Optimized conditions reveal high production yields of 89Zr ~ 37 ± 1.4 MBq/µA using 89Y(p,n)89Zr, ~ 12.7 MeV of proton, and 35 µA using yttrium coin target with indigenously constructed 30 MeV Cyclotron (RFT-30). Besides, the production optimization, quality control, and biological behavior of [89Zr]Zr-oxalate, chloride and, DFO demonstrated promising results. [ABSTRACT FROM AUTHOR]

Background: Both elevated blood homocysteine and diabetes mellitus (DM) are related to cognitive impairments or dementia. A previous study also demonstrated that the association between homocysteine and cognitive decline was much stronger in individuals with DM than in those without DM.Objective: This study aimed to examine the interactive effect of blood homocysteine and DM on brain pathological changes including brain atrophy, amyloid-β and tau deposition, and small vessel disease (SVD) related to cognitive impairments.Methods: A total of 430 non-demented older adults underwent comprehensive clinical assessment, measurement of serum homocysteine level, [11C] Pittsburgh Compound B (PiB) PET, [18F] AV-1451 PET, and brain MRI.Results: The interactive effect of homocysteine with the presence of DM on brain atrophy, especially in aging-related brain regions, was significant. Higher homocysteine concentration was associated with more prominent brain atrophy in individuals with DM, but not in those without DM. In contrast, interaction effect of homocysteine and DM was found neither on Alzheimer's disease (AD) pathologies, including amyloid-β and tau deposition, nor white matter hyperintensity volume as a measure of SVD.Conclusion: The present findings suggest that high blood homocysteine level and DM synergistically aggravate brain damage independently of AD and cerebrovascular disease. With regard to preventing dementia or cognitive decline in older adults, these results support the importance of strictly controlling blood glucose in individuals with hyperhomocysteinemia and lowering blood homocysteine level in those with DM. [ABSTRACT FROM AUTHOR]

Background: Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with in vivo AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies. Methods: A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured. Results: A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect. Conclusion: The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures. [ABSTRACT FROM AUTHOR]

Tinnitus is a conscious auditory perception in the absence of an external stimulus. Despite previous reports of a recognized association between tinnitus and cognitive deficits, the effects of tinnitus on functional and structural brain changes associated with cognitive deficits remain unknown. We aimed to investigate the changes in glucose metabolism and gray matter (GM) volume in subjects diagnosed with mild cognitive impairment (MCI) depending on tinnitus. Twenty-three subjects were subclassified into MCI with the chronic tinnitus (MCI_T) and MCI without tinnitus (MCI_NT) groups. Encouraged by the identification of neural substrates associated with tinnitus and cognitive deficits, we correlated the extent of tinnitus severity with the changes in glucose metabolism and GM volume and conducted a glucose metabolic connectivity study. Compared to the MCI_NT group, the MCI_T group showed significantly lower metabolism in the right superior temporal pole and left fusiform gyrus. Additionally, the GM volume in the right insula was markedly lower in the MCI_T group compared to the MCI_NT group. Moreover, correlation analyses in metabolism or GM volumes revealed specific brain regions associated with the cognitive decline with increasing tinnitus severity. Metabolic connectivity analysis revealed that MCI_NT had markedly strengthened intra-hemispheric connectivity in the frontal, parietal, and occipital regions than did MCI_T. Furthermore, MCI_NT showed a strong negative association between the parietal and temporal and parietal and limbic regions, but the association was not observed in MCI_T. These findings indicate that tinnitus may cause metabolic and structural changes in the brain and alters complex inter- or intra-hemispheric networks in MCI. Considering the impact of MCI on accelerating dementia, these results provide a valuable basis on which yet-to-be-identified neurodegenerative markers of tinnitus can be refined. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated an association between Alzheimer's disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10μm (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association.Objective: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging.Methods: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11C-Pittsburg compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10μm over the past 5 years (PM10mean) collected from air pollution surveillance stations were matched to each participant's residence.Results: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-β (Aβ) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure.Conclusion: The findings suggest that long-term exposure to PM10 may contribute to pathological Aβ deposition. [ABSTRACT FROM AUTHOR]

Aim: It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD‐related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid‐beta (Aβ) burden, AD‐signature regional neurodegeneration, and white matter hyperintensities (WMH) in non‐demented middle‐ and old‐aged adults. Methods: A total of 397 non‐demented participants underwent comprehensive clinical and neuropsychological assessments, 11C‐labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five‐Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. Results: Neither neuroticism nor conscientiousness was associated with cerebral Aβ deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD‐signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD‐signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aβ deposition or WMH were not. Conclusion: The present findings suggest that amyloid‐independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD. [ABSTRACT FROM AUTHOR]

Background: An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aβ) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aβ deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain.Methods and Findings: The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aβ positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history.Conclusions: In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aβ deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury. [ABSTRACT FROM AUTHOR]

A durable and ready to use 68Ge-68Ga generator column material is required for its routine use in radiopharmaceutical procedures. The present work comprises preliminary studies for development and evaluation of chitosan-TiO 2 based microsphere (C-TOM) composite towards its competence as a column material. The batch uptake studies showed higher distribution coefficients for 68Ge vis-à-vis 68Ga in the complete concentration range of HCl examined (0.01–1 mol.L−1). Furthermore, C-TOM showed enduring physical and chemical stability in 0.01 mol.L−1 HCl with persistent 68Ga elution profiles (>95%) and negligible 68Ge breakthrough (2 × 10−4%) for the preliminary evaluation period of ∼2 months. Overall, the studies indicated that, 68Ga with high radionuclidic purity (≥99.99%) can be eluted routinely in a small volume (∼1.5 mL) of 0.01 mol.L−1 HCl proving its potentials as a novel solid phase extractant for 68Ge/68Ge generator system. Image 1 • Novel approach towards synthesis of chitosan-TiO 2 microsphere (C-TOM). • Superlative physical and chemical stability of C-TOM in 0.01 M HCl. • Separation of 68Ga from 68Ge with high radionuclidic purity. • Consistent 68Ga elution profile with low 68Ge breakthrough. • Possible application of C-TOM as a potential 68Ge/68Ga generator material. [ABSTRACT FROM AUTHOR]

This study tested the efficacy of the phosphodiesterase type III inhibitor cilostazol in Alzheimer's disease patients with white matter lesions treated with donepezil in comparison with donepezil monotherapy using fluorodeoxyglucose (18F) positron-emission tomography (FDG PET). A 24-week, randomized, double-blind, placebo-controlled, parallel-group study was conducted. Thirty-six Alzheimer's disease patients with white matter lesions who received donepezil (n = 18 each in the cilostazol and placebo groups) were enrolled. Participants underwent pre and post FDG PET imaging scans and three rounds of clinical and neuropsychological tests. The cilostazol group did not show a significant decrease of regional glucose metabolism; however, regional glucose metabolism was significantly decreased in the parietal and frontal lobes of the placebo group. The repeated measures ANOVA measuring differences in uptake change revealed that regional glucose metabolism in the left inferior frontal gyrus was significantly more preserved in the cilostazol group than that in the placebo group (p < 0.005). Mean changes from baseline on the Mini-Mental State Exam, Alzheimer's Disease Assessment Scale-cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory, and the Clinical Dementia Rating Sum of Boxes did not differ between the two groups. In the cilostazol group, the increase of glucose metabolism correlated with the improvment of the Alzheimer's Disease Assessment Scale-cognitive score. We conclude that cilostazol treatment added to donepezil may delay the decline in regional cerebral metabolism in Alzheimer's disease with white matter lesions compared with donepezil monotherapy. In additon, our results verified the efficacy of cilostazol in improving or protecting cognitive function in Alzheimer's disease through increased glucose metabolism. However, the long-term effect of cilostazol on cognitive function and Alzheimer's disease modification must be tested in further studies with larger sample size and longer study period. Trial registration: http://clinicaltrials.gov : NCT01409564. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to find peripheral biomarkers and central metabolites affecting neuroinflammation in complex regional pain syndrome (CRPS) patients using [11C]-(R)-PK11195 positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Methods Using MRS and PET, we measured associations between neurometabolites and neuroinflammation in 12 CRPS patients and 11 healthy controls. Also, we investigated various peripheral parameters that may affect neuroinflammation in CRPS. Results We found positive correlations of Lipid (Lip)13a/total creatine (tCr) and Lip09/tCr with neuroinflammation, the distribution volume ratio (DVR) of [11C]-(R)-PK11195 in the right and left insula in CRPS patients. However, these correlations were not found in controls. High hemoglobin levels correlated with decreased neuroinflammation (the DVR of [11C]-(R)-PK11195) in the right thalamus and left insula in healthy controls. We found that high levels of glucose and pH correlated with increased neuroinflammation, but high levels of CO2, basophil, and creatinine were associated with decreased neuroinflammation in the left thalamus and the right and left insula in CRPS patients. Conclusions This is the first report indicating that elevated neuroinflammation levels are associated primarily with lipids in the brain and pH, glucose, CO2, basophil, and creatinine in the peripheral parameters in CRPS patients. Our results suggest that characterizing the peripheral biomarkers and central metabolites affecting neuroinflammation is essential to understanding the pathophysiology of CRPS. [ABSTRACT FROM AUTHOR]

Background: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful to predict Alzheimer’s disease (AD) conversion in patients with mild cognitive impairment (MCI). However, few studies have examined the extent to which FDG PET alone can predict AD conversion and compared the efficacy between visual and computer-assisted analysis directly.Objective: The current study aimed to evaluate the value of FDG PET in predicting the conversion to AD in patients with MCI and to compare the predictive values of visual reading and computer-assisted analysis.Methods and materials: A total of 54 patients with MCI were evaluated with FDG PET and followed-up for 2 years with final diagnostic evaluation. FDG PET images were evaluated by (1) traditional visual rating, (2) composite score of visual rating of the brain cortices, and (3) composite score of computer-assisted analysis. Receiver operating characteristics (ROC) curves were compared to analyze predictive values.Results: Nineteen patients (35.2%) converted to AD from MCI. The area under the curve (AUC) of the ROC curve of the traditional visual rating, composite score of visual rating, and computer-assisted analysis were 0.67, 0.76, and 0.79, respectively. ROC curves of the composite scores of the visual rating and computer-assisted analysis were comparable (Z = 0.463, p = 0.643).Conclusions: Visual rating and computer-assisted analysis of FDG PET scans were analogously accurate in predicting AD conversion in patients with MCI. Therefore, FDG PET may be a useful tool for screening AD conversion in patients with MCI, when using composite score, regardless of the method of interpretation. [ABSTRACT FROM AUTHOR]

Accumulation of triphenylphosphonium (TPP) is normally observed in the mitochondria from the extracellular spaces due to the high difference in plasma membrane potential of the mitochondria. In the cancer cells, the mitochondrial membrane potential gap is higher as compared to that of normal cells resulting in elevated uptake of TPP. Silica nanoparticles (SNPs) being widely developed and used for biomedical applications, in this study, we tried to modify the surface of SNPs with varying amounts of TPP to verify their possible application as a positron emission tomography (PET) agent. The studies confirmed that the high level of TPP loading on the surface of SNPs possess higher positive charge (+ 31.5 mV). Owing to this behavior of plasma membrane potential of cancerous cells the uptake of positively charged SNPs was much higher in tumor cells than that of normal cells which was confirmed by PET imaging. [ABSTRACT FROM AUTHOR]

68Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [68Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7. [ABSTRACT FROM AUTHOR]

Exposure to diesel particulate matter (DPM) is associated with several adverse health effects, including severe respiratory diseases. Quantitative analysis of DPM in vivo can provide important information on the behavior of harmful chemicals, as well as their toxicological impacts in living subjects. This study presents whole-body images and tissue distributions of DPM in animal models, using molecular imaging and radiolabeling techniques. The self-assembly of the 89Zr-labeled pyrene analog with a suspension of DPM efficiently produced 89Zr-incorporated DPM (89Zr-DPM). Positron emission tomography images were obtained for mice exposed to 89Zr-DPM via three administration routes: intratracheal, oral, and intravenous injection. DPM was largely distributed in the lungs and only slowly cleared after 7 days in mice exposed via the intratracheal route. In addition, a portion of 89Zr-DPM was translocated to other organs, such as the heart, spleen, and liver. Uptake values in these organs were also noticeable following exposure via the intravenous route. In contrast, most of the orally administered DPM was excreted quickly within a day. These results suggest that continuous inhalation exposure to DPM causes serious lung damage and may cause toxic effects in the extrapulmonary organs. [Display omitted] • A89Zr-labeling method was used for tracing diesel particulate matter (DPM) in mice. • 89Zr-incorporated DPM was administered in mice via three different routes. • When exposed via the intratracheal route, DPM was highly distributed in the lungs and excreted slowly. • Uptake in some organs such as spleen and heart were evident following intravenous exposure. • Most of the orally administered diesel particulates were cleared quickly in a day. [ABSTRACT FROM AUTHOR]

In this study, we investigated the tumor targeting effect in cancer cells using triphenylphosphonium (TPP) cations, which are accumulated by differences in membrane potential, and folic acid (FA), which is selectively bound to overexpressed receptors on various cancer cells. We used Food and Drug Administration (FDA)-approved silica nanoparticles (SNPs) as drug carriers, and SNPs conjugated with TPP and FA (STFs) samples were prepared by introducing different amounts of TPP and FA onto the nanoparticle surfaces. STF-1, 2, 3, 4 and 5 are named according to the combination ratio of TPP and FA on the particle surface. To confirm the tumor targeting effect, 89Zr (t1/2 = 3.3 days) was coordinated directly to the silanol group of SNP surfaces without chelators. It was shown that the radiochemical yield was 69% and radiochemical purity was >99%. In the cellular uptake evaluation, SNPs with the most TPP (SFT-5) and FA (SFT-1) attached indicated similar uptake tendencies for mouse colon cancer cells (CT-26). However, the results of the cell internalization assay and measurement of positron emission tomography (PET) images showed that SFT-5 had more affinity for the CT-26 tumor than other samples the TPP ratio of which was lower. Consequently, we confirmed that TPP ligands affect target cancer cells more than FA, which means that cell membrane potential is significantly effective for tumor targeting. [ABSTRACT FROM AUTHOR]

Background: Cognitive frailty and impairment are phenotypically and pathophysiologically correlated with physical frailty. We examined associations between accumulation of amyloid-β in the brain as a brain imaging biomarker and phenotypes of physical frailty (weight loss, weakness, exhaustion, slowness, low physical activity) in older adults with mild cognitive impairment (MCI) and cognitive frailty. Methods: Cross-sectional associations between brain amyloid-β accumulation measured with 11C-Pittsburgh compound B (PiB)-positron emission tomography (PET) and physical frailty were examined in 48 elderly participants (mean age: 75.1 ± 6.6 years; 73% female). Cortical and regional standard uptake value ratios (SUVRs) were obtained. Main outcome measures included frailty phenotypes and physical functions (gait speed, short physical performance battery, and Timed Up and Go tests). Results: Mean cortical region of interest and regional SUVRs (frontal cortex, temporal cortex, parietal cortex, precuneus/posterior cingulate cortex (PC/PCC), hippocampus, basal ganglia, and global SUVR) were associated with gait speed, Timed Up and Go, and short physical performance battery (PC/PCC, basal ganglia). In addition, SUVRs of all brain regions were significantly linked to weakness. Conclusion: SUVRs of all brain regions revealed an association between brain amyloid-β accumulation and weakness. Furthermore, global SUVRs (frontal cortex, temporal cortex, parietal cortex, PC/PCC, hippocampus, basal ganglia) were associated with gait parameters. [ABSTRACT FROM AUTHOR]

• MicroRNA-485-3p concentrations in salivary EE-EVs were increased in the patients with AD vs. those in healthy controls. • MicroRNA-485-3p concentrations from salivary EE-EVs were increased in Aβ-PET-positive AD participants vs. those in Aβ-PET-negative AD participants. • MicroRNA-485-3p concentrations from salivary EE-EVs showed high diagnostic accuracy for predicting Aβ-PET positivity. Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive long-term memory loss and cognitive dysfunction. Neuroimaging tests for abnormal amyloid-β (Aβ) deposition are considered the most reliable methods for the diagnosis of AD; however, the cost for such testing is very high and generally not covered by national insurance systems. Accordingly, it is only recommended for individuals exhibiting clinical symptoms of AD supported by clinical cognitive assessments. Recently, it was suggested that dysregulated microRNA-485-3p (miRNA-485-3p) in the brain and cerebrospinal fluid is closely related to pathogenesis of AD. However, a relationship between circulating miRNA-485-3p in salivary exosome-enriched extracellular vesicles (EE-EV) and Aβ deposition in the brain has not been observed. Using quantitative real-time polymerase chain reaction, we analyzed miRNA-485-3p concentration in salivary EE-EV. We used receiver operating characteristic (ROC) curve analysis to evaluate its predictive value for Aβ positron emission tomography (Aβ-PET) positivity in patients with AD. Our results showed that the miRNA-485-3p concentration in salivary EE-EV isolated from patients with AD was significantly increased compared with that in the healthy controls (p < 0.0001). In the analysis of all participants, the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive participants compared to Aβ-PET-negative participants (p < 0.0001). Further analysis using only AD patients also showed that the miRNA-485-3p concentration was significantly increased in Aβ-PET-positive AD patients vs. Aβ-PET-negative AD patients (p = 0.0063). The ROC curve analysis for differentiating Aβ-PET-positive and negative participants showed that the area under the curve for miRNA-485-3p was 0.9217. These findings suggested that the miRNA-485-3p concentration in salivary EE-EV was closely related to Aβ deposition in the brain and had high diagnostic accuracy for predicting Aβ-PET positivity. [ABSTRACT FROM AUTHOR]