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INTRODUCTION: Despite prior research on the association between sarcopenia and cognitive impairment in the elderly, a comprehensive model that integrates various brain pathologies is still lacking. METHODS: We used data from 528 non‐demented older adults with or without sarcopenia in the Catholic Aging Brain Imaging (CABI) database, containing magnetic resonance imaging scans, positron emission tomography scans, and clinical data. We also measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five times sit‐to‐stand test (5STS). RESULTS: All components of sarcopenia were significantly correlated with global cognitive function, but cortical thickness and amyloid‐beta (Aβ) retention had distinctive relationships with each measure. In the path model, brain atrophy resulting in cognitive impairment was mediated by Aβ retention for SMI and periventricular white matter hyperintensity for HGS, but directly affected by the 5STS. DISCUSSION: Treatments targeting each sub‐domain of sarcopenia should be considered to prevent cognitive decline. Highlights: We identified distinct impacts of three sarcopenia measures on brain structure and Aβ.Muscle mass is mainly associated with Aβ and has an influence on the brain atrophy.Muscle strength linked with periventricular WMH and brain atrophy.Muscle function associated with cortical thinning in specific brain regions.Interventions on sarcopenia may be important to ease cognitive decline in the elderly. [ABSTRACT FROM AUTHOR]

Exercise has long been recognized as an important component of treatment for various diseases. However, the benefits and risks of exercise interventions must be carefully evaluated to ensure the former outweighs the latter. As cancer patients undergo diverse treatment modalities with distinct objectives, a systematic approach partitioning the cancer journey into distinct phases is necessary to inform tailored exercise prescriptions. This narrative review summarizes exercise benefits and mechanisms for cancer patients and survivors across four distinct survivorship periods--before surgery, after surgery and before adjuvant treatment, during nonsurgical treatment (adjuvant and neoadjuvant), and during extended survival. In summary, exercise reduces the risks of complications and declines in physical functioning while improving fatigue, quality of life, and the ability to manage treatment effects. Although additional research is warranted, existing evidence is sufficient to integrate exercise into clinical oncology practice and cancer survivorship programs. [ABSTRACT FROM AUTHOR]

Background: Multi‐modality data can achieve better classification and regression performance than the use of only the single modality data. For this reason, we observed the potential of multiple data for early dementia conversion. Method: In this study, the conversion group was defined as cases where MCI patients converted to dementia between 2 and 4 years, and T1‐weighted, T2 FLAIR, and Amyloid PET images were acquired from 4 domestic hospitals and ADNI. 114 volume features, WMH volume, and Fazekas scale were acquired from T1, T2 FLAIR images, and SUVR was calculated from amyloid PET. In addition to image features, age, sex, MMSE, and ApoE genotype were used. The 206 cases dataset was divided in a stratified way into a training set (80%) and testing set (20%), keeping the sample percentage of each class in both sets. We wanted to check the performance of each model on our dataset. The models used for this purpose were Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), Linear Regression Classifier (LR), Gradient Boosting Model (GBM), Extreme Gradient Boosting (XGB). We trained and tuned each model, set up a grid search through hyperparameters to select a model that generalized well. The metrics used to evaluate model performance were BA, SE, SP, and AUC. Result: Table 2 and 3 present the obtained results of all ML models for the two‐class classification task using 10‐fold cross‐validation and testing. In the case of 10‐fold cross‐validation, the model with highest mean BA was the SV model with 0.927. However, in the case of testing, we can see in Table 3 that the model with the highest BA, SE, and SP obtained was the GBM model, which was 0.917, 0.900, and 0.933, respectively. When ensemble was performed using the top3 models, BA, SE, SP, and AUC of the ensemble model were 0.917, 0.900, 0.933, and 0.963, respectively. Conclusion: Muti‐modal neuroimaging features with minimal demographic information showed reliable results in predicting the converters and non‐converters between 2 and 4 years. This study suggests it could be utilized for future clinical trials to provide a high‐risk group for dementia conversion in advance. [ABSTRACT FROM AUTHOR]

We study a successful model to explain the muon anomalous magnetic moment originating from Yukawa-type interactions in a supersymmetric theory. Thanks to a modular A 4 flavor symmetry, any lepton flavor violations that spoil the model are forbidden. We also investigate a predictive radiative seesaw model including a dark matter (DM) candidate. At first, we construct the minimum model to satisfy the neutrino oscillation data and obtain several predictions such as Dirac CP and Majorana phases, the neutrino masses through χ 2 analysis. However, the minimum model would not provide our promising DM candidate. Thus, we minimally extend the model and find a good DM candidate. In the extended framework, we show the allowed regions to satisfy the muon anomalous magnetic moment and the observed relic density of dark matter in addition to predictions of the lepton sector. [ABSTRACT FROM AUTHOR]

Background: Multimer detection system‐oligomeric amyloid‐ß (MDS‐OAß) measures plasma OAß level and is associated pathology of Alzheimer's disease (AD). However, no study investigated MDS‐OAß and cerebral Aß deposition among difference stages within AD spectrum. Method: We studied 40 normal control (CN), 30 amyloid‐PET (A‐PET) negative mild cognitive impairment (MCI), 31 A‐PET positive MCI, and 22 A‐PET positive dementia. Result: The one‐way analysis of variance showed group difference in MDS‐OAß. Post‐hoc analysis showed that MDS‐OAß was lowest in CN group and highest in A‐PET positive MCI group. Both A‐PET negative MCI and A‐PET positive dementia groups showed lower MDS‐OAß than A‐PET positive group dementia group (MDS‐OAß: CN < A‐PET negative MCI = A‐PET positive dementia < A‐PET positive MCI) (Figure 1). MDS‐OAß showed a positive correlation with global and regional cerebral Aß deposition measure using A‐PET. Conclusion: Our results suggest that MDS‐OAβ shows a reverse U‐shape: increase with disease onset or when clinical symptoms appear, even before Aß pathology is evident in A‐PET, and then elevate as disease progresses but lower down as the disease becomes severe. [ABSTRACT FROM AUTHOR]

A 40 nm complementary metal oxide semiconductor carrier‐aggregated drive amplifier with high linearity is presented for sub‐GHz Internet of Things applications. The proposed drive amplifier consists of two high linear amplifiers, which are composed of five differential cascode cells. Carrier aggregation can be achieved by switching on both the driver amplifiers simultaneously and combining the two independent signals in the current mode. The common gate bias of the cascode cells is selected to maximize the output 1 dB compression point (P1dB) to support high‐linear wideband applications, and is used for the local supply voltage of digital circuitry for gain control. The proposed circuit achieved an output P1dB of 10.7 dBm with over 22.8 dBm of output 3rd‐order intercept point up to 0.9 GHz and demonstrated a 55 dBc adjacent channel leakage ratio (ACLR) for the 802.11af with −5 dBm channel power. To the best of our knowledge, this is the first demonstration of the wideband carrier‐aggregated drive amplifier that achieves the highest ACLR performance. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated the pivotal implications of the locus coeruleus (LC) and in the early phase of Alzheimer's disease (AD). However, the effects of apolipoprotein E4(APOE4) carrier status on the LC functional connectivity (FC) in preclinical AD remain elusive. We aimed to demonstrate disparities in LC FC in preclinical AD with regard to APOE4 carrier status. Methods: A total of 112 patients with who were amyloid beta (Aβ) positive([18F] flutemetamol +) were recruited in the study, and they all had normal cognition. Seed to voxel analysis was conducted to measure LC FC differences between APOE4 non‐carrier and carrier. In addition, group by amyloid beta (Aβ) interactive effects on FC values were analyzed with a general linear model. Result: The LC FC with intracalcarine cortex, lingual gyrus, occipital fusiform gyrus of the both hemispheres was reduced in APOE4 carrier. Moreover, there was a statistically significant group by regional standardized uptake value ratio interactions in LC FC with frontal, occipital cortices, the precuneus and the cerebellum. Conclusion: The aforementioned findings suggest that there are differential patterns of LC FC in APOE4 non‐carrier and carrier with preclinical AD, which interact with regional Aβ deposition. [ABSTRACT FROM AUTHOR]

Background: An electrical field (EF) strength induced by tDCS affects a therapeutic effect. Additionally, sequential tDCS has improved white matter integrity in cognitively impaired patients. However, researchers have not evaluated the impact of EF strength on white matter integrity in the prodromal stage of dementia. This study aimed to elucidate the effect of EF strength from prefrontal anodal tDCS on white matter integrity change and the modulating role of relevant genetic and pathologic factors in this effect in amnestic mild cognitive impairment (MCI) patients. Method: In 55 amnestic MCI patients, we delivered anodal‐tDCS (2 mA/day, five times/week, for two weeks) over the left dorsolateral prefrontal cortex (DLPFC), calculated the EF strength for the left inferior frontal gyrus and DLPFC through the stimulation navigation program analysis. Additionally, we assessed the white matter integrity by diffusion tensor imaging before and after two weeks of stimulation; finally, we evaluated the modulating factors: amyloid‐beta (Aβ) deposition, APOE ε4‐allele status, and BDNF polymorphism. Result: As the EF intensity in the left inferior frontal gyrus increased, the range of changes in white matter integrity significantly increased in left anterior thalamic radiation, corticospinal tract, inferior fronto‐occipital fasciculus, and inferior longitudinal fasciculus. Additionally, we found that greater change in white matter integrity was observed with higher regional EF strength in the APOE ε4 non‐carriers and BDNF MET non‐carrier, which could be attributed to an interaction between these modulating factors and EF intensity in the left anterior thalamic radiation and right uncinate fasciculus. Conclusion: These findings provide evidence for the precision‐medicine‐based application of tDCS in the prodromal stage of dementia, inducing the optimized therapeutic effect. [ABSTRACT FROM AUTHOR]

The utilization of clathrate hydrates as a highly promising technology for CO 2 capture and separation is the focus of this review paper. We present an in-depth exploration of hydrate-based CO 2 capture technology, highlighting the use of various additives to enhance the performance of CO 2 hydrate formation, as well as the separation and capture of CO 2 from gas mixtures containing N 2 /H 2 /CH 4. By employing thermodynamic promoters, CO 2 molecules can efficiently occupy hydrate cages under moderate temperature and pressure conditions, while kinetic promoters improve the kinetic properties of hydrate formation. Key performance indicators such as (normalized) gas uptake, t 90 , and separation factor are comprehensively discussed and summarized. Moreover, this review introduces additional applications of CO 2 hydrates, such as their potential in cold energy storage due to their high heat of formation (∆ H d) of approximately 500 kJ/kg, surpassing that of ice at 333 kJ/kg. Additionally, we explore the advantages of the CH 4 -CO 2 replacement method, which offers an energy production alternative without the drawbacks of sediment subsidence and ecosystem destruction. Through a comprehensive review, we emphasize the potential of clathrate hydrates as a promising technology for CO 2 capture and underscore the importance of further research in this area. Ultimately, CO 2 hydrates represent a future direction for mitigating global warming. [Display omitted] • Various thermodynamic and kinetic hydrate promoters were explored. • Gas separation performances of hydrate-based technologies were summarized. • Potential of cold energy storage material with high dissociation enthalpy was addressed. • Various studies of CH 4 -CO 2 replacement were introduced. [ABSTRACT FROM AUTHOR]

Objective This study aims to evaluate the prognosis of single cantilevered restoration, of which the cantilever length is less than 6 mm, retrospectively. Methods This study targeted 33 patients (20 males, 13 females) who were treated with total 35 single cantilevered restorations (mesial direction or distal direction) combined with implant installations from May 2004 to December 2012. All of the implant prostheses were single implant–supported and cantilevered(cantilever lengths were over 3 mm). Results The length of cantilevers ranged from 3.01 mm to 5.99 mm. All implants survived during the average of 47.72 months of observation period. The success rate of implants was 94.29%. The complications were peri-implantitis (8.57%) with symptoms such as swelling and bleeding and prosthetic complications (22.9%) such as screw loosening, abutment hex fracture, screw locking, and crown fracture. There was an average of 0.04 ± 0.14 mm peri-implant alveolar bone loss at 1 year after loading and 0.16 ± 0.51 mm at final observation. Conclusions Although single cantilevered restoration shorter than 6 mm does not induce crestal bone loss around the implant, several complications such as peri-implantitis and mechanical complications could still remain. [ABSTRACT FROM AUTHOR]

Background and Aims Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors. Methods One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise ( n = 62) or standard care control group ( n = 61) for 12 weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining ≥ 18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in > 18 MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-α levels and 6 min walk distance from baseline to post-intervention. Results After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1 ± 14.7 MET-h/wk. to 26.6 ± 21.7 MET-h/wk. in the exercise group, with no change in the control group ( p < 0.01 for group and time interaction). Circulating insulin level decreased by 1 μU/ml (6.0 ± 3.9 vs. 5.0 ± 3.5, p = 0.009) in the exercise group with no change in the control group ( p = 0.022 for group and time interaction). A similar trend was observed in TNF-α ( p = 0.030 for group and time interaction). Six minute walk distance increased by 25.2 m in the exercise group with no change in the control group ( p = 0.061 for group and time interaction). Conclusions The 12 week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence suggests a deteriorating effect of subthreshold amyloid‐beta (Aβ) accumulation before the onset of clinical symptoms of Alzheimer's disease (AD). Despite the association between the Aβ‐dependent pathway and the APOE ε4 allele, the modulating impact of this allele on the associations between subthreshold Aβ retention, cortical atrophy, and neuropsychological performance is unclear. This study aimed to explore the differential effect of the APOE ε4 allele on the association between subthreshold Aβ retention, cortical volume, and cognitive performance in cognitively healthy older adults (CN). Method: A total of 112 CN with subthreshold Aβ retention, consisting of 80 APOE ε4 non‐carrier and 32 APOE ε4 carrier, were included in the study. Participants underwent structural magnetic resonance imaging, [18F] flutemetamol (FMM) PET‐CT, and neuropsychological battery. Potential interactions between APOE status and Aβ accumulation were assessed with F‐tests implemented on both linear and quadratic interaction terms, adjusting for age, sex, and education years. Result: We found a significant interaction between APOE ε4 allele, subthreshold Aβ deposits, cognitive function for cortical volume of predefined brain regions vulnerable to early Aβ retention. In CN with APOE ε4 carrier, regional Aβ retention in frontal, parietal, temporal lobe, and posterior cingulate cortex/precuneus showed a U‐shaped relationship with cortical volumes of superior parietal, fusiform gyrus, and amygdala. Furthermore, cortical volumes of superior, inferior temporal lobe, and parahippocampal gyrus in APOE ε4 carrier displayed a U‐shaped relationship with attention and executive function scores. Conclusion: This study is the first attempt to thoroughly examine the mechanism at play in the earliest phase of Alzheimer's disease, focusing on the influence of the APOE ε4 allele on the association between subthreshold Aβ retention and cortical volume during the preclinical phase. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence suggests a deteriorating effect of sub‐threshold amyloid‐beta (Aβ) accumulation on cognition before the onset of clinical symptoms of Alzheimer's disease. Despite the association between the Aβ‐dependent pathway and the APOE ε4 allele, the impact of this allele on the progression from the sub‐threshold Aβ deposits to cognitive function impairment is unclear. Furthermore, the comparative analysis of positive Aβ accumulation in the preclinical phase is lacking. This study aimed to explore the differential effect of the APOE ε4 allele on the association between Aβ retention, brain function, and cognitive performance in cognitively healthy older adults, depending on the Aβ burden status. Method: One hundred and eighty‐two older adults with normal cognition who underwent resting‐state functional magnetic resonance imaging were enrolled. They were dichotomized using [18F]‐labeled flutemetamol positron emission tomography into subjects with sub‐threshold (cognitively normal [CN] sub‐Aβ, n = 110; [APOE ε4 carrier, n = 30; non‐carrier, n = 80] and positive Aβ deposits [CN Aβ+ group, n = 72; APOE ε4 carrier, n = 34; non‐carrier, n = 38]). Result: We found (i) distinct effects of the APOE ε4 allele and relationships with cognitive function in the preclinical phase; (ii) differences in local functional connectivity (FC) of the brain regions in networks vulnerable to Alzheimer's disease according to the APOE ε4 allele, which was associated with higher executive and memory function; (iii) a differential association between regional Aβ retention and local FC according to the APOE ε4 allele; and (iv) a significant interaction between APOE ε4 allele and local FC for the remote inter‐network FC between the default‐mode and central‐executive network in the CN sub‐Aβ group, contributing a compensatory role for cognitive performance. Finally, these results were modulated according to Aβ positivity. Conclusion: This study is the first attempt to thoroughly examine the mechanism at play in the earliest phase of Alzheimer's disease, focusing on the influence of the APOE ε4 allele from the sub‐threshold to positive Aβ retention during the preclinical phase. [ABSTRACT FROM AUTHOR]

The hydrate formation rate and conversion yield are essential factors for hydrate-based gas storage and accordingly various thermodynamic and kinetic promoters have been extensively investigated. However, for hydrate-based CO 2 capture, carbonate ions induced from dissolved CO 2 in water hinder the performance of kinetic promoters (e.g., sodium dodecyl sulfate (SDS)). In this work, we introduce a superabsorbent polymer (SAP) matrix that provides an extremely high interfacial area between a sorbed tetrahydrofuran (THF) solution and gaseous CO 2. The SAP enhanced the formation rate of binary THF-CO 2 hydrate, despite the absence of mechanical agitation. We varied the concentration of THF, temperature, reactor volume, and the ratio of solution to the reactor for a systematic study and explored their effects on the CO 2 storage capacity and the induction time. We observed that highly concentrated THF and a larger reactor with a high gas-liquid contact area enhanced the CO 2 storage capacity and formation rate. Raman and PXRD spectroscopic analyses were employed to investigate the guest distribution and crystalline structure of the THF-CO 2 hydrates synthesized under various conditions. All the binary hydrates were structure-II (sII) hydrates, and there was no pure structure-I (sI) CO 2 hydrate. Based on the spectroscopic results, we developed a theoretical model that could calculate the amount of enclathrated CO 2 and dissolved CO 2 in liquid phases separately. This work reveals that SAP has excellent potential for rapid CO 2 capture in hydrate media with a high water-to-hydrate conversion ratio. • Dispersion of binary THF-CO 2 hydrates in SAP enhanced CO 2 storage capacity. • The size effect of solution/reactor on CO 2 uptake was investigated. • CO 2 in hydrate/liquid phase was distinguished for the precise capacity calculation. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated that sub‐threshold amyloid‐beta retention is related to cognitive performance, functional brain change, and further amyloid‐beta /tau accumulation. However, little research has investigated an effect of APOE genotype on the association between sub‐threshold amyloid‐beta deposition and intra‐regional brain activity in the earliest stage of Alzheimer’s disease (AD). This study set out to evaluate the impact of sub‐threshold global and regional amyloid‐beta retention on intra‐regional brain activity, measured by regional homogeneity (ReHo), in cognitively normal older adults, according to APOE ε4‐allele status. Method: Cognitively normal older adults with and without APOE ε4 allele (carrier, n=32; non‐carrier, n=80) underwent functional magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans with [18F] flutemetamol. Whole‐brain voxel wise analysis was conducted for evaluating the sub‐threshold Ab deposition‐by‐ APOE genotype interaction for ReHo, adjusting for age, sex, and education years. Result: Sub‐threshold amyloid‐beta deposition in temporal lobe showed a significant interaction with APOE genotype for ReHo of left calcarine fissure and surrounding cortex, cerebellum 7, and cerebellum 6 (FDR‐adjusted p < 0.05, cluster size > 100 voxels). Cognitively normal older adults with APOE ε4 allele exhibited a positive relationship between sub‐threshold amyloid‐beta retention in temporal lobe and ReHo, while those without APOE ε4 allele showing an opposing association. Conclusion: Thus, even sub‐threshold amyloid‐beta deposition has a differential impact on ReHo according to the representative AD risk factor, APOE ε4 allele in the earliest phase of AD. These results could contribute to the deeper understanding of the initial pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated that sub‐threshold amyloid‐beta retention is related to cognitive performance, functional brain change, and further amyloid‐beta /tau accumulation. However, few previous studies have examined an effect of APOE genotype on the association between functional connectivity (FC) and memory performance in the earliest stage of Alzheimer’s disease (AD). We aimed to evaluate the difference in intra‐ and inter‐regional FC between cognitive older adults with and without APOE ε4‐allele and examined an impact of intra‐ and inter‐regional FC on memory performance in cognitively intact older adults, according to APOE ε4‐allele status. Method: Cognitively normal older adults with and without APOE ε4 allele (carrier, n=32; non‐carrier, n=80) underwent neuropsychological battery, resting‐state functional magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans with [18F] flutemetamol. We employed a priori defined regions of interest to investigate the intra‐ and inter‐network FC profiles of default mode network (DMN), central executive network (CEN), and salience network (SN). We evaluated difference in intra‐ and inter‐regional FC via analysis of covariance and examined the intra‐ and inter‐regional FC‐by‐APOE genotype interaction for memory performance by multiple linear regression analysis, adjusting for age, sex, and education years. Result: There was no significant difference in intra‐ and inter‐regional FC for cognitively intact older adults without amyloid‐beta retention between APOE ε4 non‐carrier and carrier. The inter‐regional FC between DMN and CEN displayed a significant interaction with APOE genotype for word list memory, total memory, and total scores (uncorrected p < 0.001; uncorrected p < 0.005; uncorrected p < 0.05). Cognitively normal older adults with APOE ε4 allele exhibited steeper slope for a positive relationship between the inter‐regional FC and memory performances than those without APOE ε4 allele. Conclusion: The inter‐regional FC between DMN and CEN has a differential impact on memory performances according to the representative AD risk factor, APOE ε4 allele in the earliest phase of AD. These results could contribute to the deeper understanding of the initial pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated that sub‐threshold amyloid‐beta retention is related to cognitive performance, functional brain change, and further amyloid‐beta/tau accumulation. However, few previous studies have assessed an effect of APOE genotype on the association between sub‐threshold amyloid‐beta deposition and cortical atrophy in the earliest stage of Alzheimer’s disease (AD). We aimed to evaluate the impact of sub‐threshold global and regional amyloid‐beta retention on cortical atrophy in cognitively normal older adults, according to APOE ε4‐allele status. Method: Cognitively normal older adults with and without APOE ε4 allele (carrier, n=32; non‐carrier, n=80) underwent structural magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans with [18F] flutemetamol. Whole‐brain voxel wise analysis was conducted for evaluating the sub‐threshold amyloid‐beta deposition‐by‐APOE genotype interaction for cortical atrophy, adjusting for age, sex, and education years. Result: Sub‐threshold amyloid‐beta deposition in posterior cingulate cortex (PCC)/precuneus showed a significant interaction with APOE genotype for gray matter volume of bilateral hippocampus, bilateral cerebellum, right middle temporal gyrus, putamen, left amygdala, postcentral, and rectus gyrus (FDR‐adjusted p < 0.001). Cognitively normal older adults with APOE ε4 allele exhibited a positive relationship between sub‐threshold amyloid‐beta retention in PCC/precuneus and normalized gray matter volume, while those without APOE ε4 allele showing an opposing association. Conclusion: Thus, even sub‐threshold amyloid‐beta deposition has a differential impact on gray matter volume according to the representative AD risk factor, APOE ε4 allele in the earliest phase of AD. These results could contribute to the deeper understanding of the initial pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Summary: In the present study, we used the SOD1G93A mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of insulin-like growth factor-binding protein 4 (IGFBP4) in the central nervous system. Decreased expression of IGFBP4 was obvious in the cerebral cortex, hippocampus, cerebellar cortex and inferior olive of SOD1G93A transgenic mice. In the cerebral cortex, there was a significant decrease in IGFBP4 immunoreactivity in the pyramidal cells. In the hippocampal formation, IGFBP4 immunoreactivity was also decreased in the pyramidal cells of CA1–3 areas and the granule cells of dentate gyrus. In the cerebellar cortex, IGFBP4 immunoreactivity was prominent in the granular layer in wtSOD1 transgenic mice, compared to that in SOD1G93A transgenic mice. IGFBP4 immunoreactivity was decreased in the inferior olive of SOD1G93A transgenic mice. This study, showing decreased IGFBP4 in different brain regions of SOD1G93A transgenic mice, may provide clues to understanding the differential susceptibility of neural structures in ALS, suggesting a role of IGFBP4 in an abnormality of cognitive and/or motor function in ALS. The mechanisms and functional implications of these decreases require elucidation. [Copyright &y& Elsevier]