bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐type deconvolution analysis of RNAseq data reveals cell‐specific glycosylation changes in the brains of Alzheimer’s Disease patients
Authors: Tang Xinyu , Lebrilla Carlito B. , Jin Lee‐Way , Maezawa Izumi , Harvey Danielle J. , Zivkovic Angela M. 
Published: June 2023

AbstractBackgroundIntriguing evidence that glycosylation is disrupted in Alzheimer’s Disease (AD) has emerged. However, our knowledge of cell‐specific alterations in the expression of genes involved in glycosylation in the brains of AD patients is limited.MethodIn this study, we conducted cell type deconvolution analysis of whole‐tissue RNAseq data to characterize cell type compositional differences and alterations in the expression of glycosylation related genes in the brains of AD patients and those with no cognitive impairment (NCI). Single‐cell human brain RNA‐seq data were obtained from the Allen Brain Map Atlas, consisting of 76,533 total nuclei derived from the cortical tissue of 2 humans. The identified cell types included GABAergic neurons, glutamatergic neurons, astrocytes, oligodendrocytes, oligodendrocyte precursor cells (OPC), microglia, endothelial cells, and vascular leptomeningeal cell (VLMC). The cell‐type deconvolution package CIBERSORT was applied in relative mode with S‐mode (single‐cell mode) batch correction to impute cell fractions and cell‐type‐specific gene expression profiles for NCI and AD samples in the ROSMAP dataset. The differences between cell type fractions of NCI and AD were analyzed by linear mixed regression model and t‐test.ResultIn the dorsolateral prefrontal cortex, neuronal cells represented the highest proportion of cells (∼30‐33%), followed by astrocytes (∼30%), and oligodendrocytes (∼20%), endothelial cells (∼7%), microglia (∼7%), VLMC (∼2‐3%), and OPC (<1%). The overall cell type composition was not significantly different between NCI and AD patients, however, the proportion of microglia, VLMC, and OPC was significantly higher in AD patients (p<0.05). The proportion of glutamatergic neuronal cells was significantly lower in female AD patients (p<0.05) compared with NCI controls, but not in males after controlling for age. Microglia‐associated expression of the glycosyltransferases MGAT1, ST6GAL1, and ST6GALNAC3 was observed in AD patients but not in NCI controls. Glutamatergic neuronal cells and VLMC cells associated with the expression of GALNT10 was observed in AD patients but not in NCI controls. In contrast, GALNT11 expression associated with astrocytes was observed in NCI controls but not in AD patients.ConclusionOur findings indicate changes in cell‐type proportions and cell‐specific changes in glycosyltransferase gene expression in the brains of AD patients compared with NCI controls.
Cyclosorus terminans extract and pioglitazone equally alleviate metabolic disturbance and brain pathology in prediabetic rats
Authors: Pratchayasakul Wasana , Chattipakorn Kenneth , Siri‐Angkul Natthapat , Choovuthayakorn Jirachaya , Charumporn Thanapat , Ongnok Benjamin , Saiyasit Napatsorn , Janjek Sornram , Arunsak Busarin , Chunchai Titikorn , Songtrai Sujinda , Kaewsuwan Sireewan , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: June 2023

AbstractBackgroundLong‐term high‐fat diet consumption causes prediabetic conditions with brain pathology, as indicated by peripheral and brain insulin resistance, neuroinflammation, neuronal necroptosis, microglial and astrocyte hyperactivation and increased Alzheimer’s disease‐related proteins including amyloid precursor protein (APP). Although pioglitazone, a peroxisome proliferator‐activated receptor (PPAR)‐γ agonist clinically used to treat type 2 diabetes mellitus, has been shown to improve the metabolic and brain functions in prediabetic condition, this drug can lead to several adverse effects. Recently, an in vitro study showed that Cyclosorus terminans extract, which acts as a natural PPAR‐γ agonist, possessed anti‐diabetic and anti‐obesity properties in adipose‐derived stem cells. However, the comparative efficacy of Cyclosorus terminans extract and pioglitazone on metabolic and brain functions in the prediabetic model has not been elucidated.MethodThirty male rats were fed with either a normal diet (ND) or a high‐fat diet (HFD) for 14 weeks. At week 13, ND‐fed rats received vehicle (NDV; n = 6) for additional 2 weeks. HFD‐fed rats were divided into four subgroups to receive either vehicle (HFV; n = 6), 100 mg/kg/day of Cyclosorus terminans extract (I‐100; n = 6), 200 mg/kg/day of Cyclosorus terminans extract (I‐200; n = 6); or 20 mg/kg/day of pioglitazone (Pio; n = 6) for additional 2 weeks. At the end of experimental period, blood and brains were collected to determine metabolic and brain functions.ResultHFD‐fed rats exhibited a prediabetic condition as characterized by obesity with peripheral insulin resistance. In addition, neuroinflammation, neuronal necroptosis, microglial and astrocyte hyperactivation, and APP expression significantly increased in HFD‐induced prediabetic rats. Cyclosorus terminans extract (100 mg/kg/day) did not attenuate the metabolic disturbance and brain pathologies in HFD‐induced prediabetic rats. Interestingly, 200 mg/kg/day of Cyclosorus terminans extract and pioglitazone equally attenuated peripheral insulin resistance, neuroinflammation, neuronal necroptosis, microglial and astrocyte hyperactivation, and APP expression in HFD‐induced prediabetic rats (P < 0.05, Figure 1).ConclusionThese findings suggest that Cyclosorus terminans extract may be another therapeutic approach for improving metabolic and brain functions in prediabetic patients who have contraindications to pioglitazone therapy.
Free recall versus combined cued recall and recognition to detect true memory impairment on the Montreal Cognitive Assessment
Authors: Wit Liselotte De , Goldstein Felicia C , Loring David W. 
Published: June 2023

AbstractBackgroundThe Montreal Cognitive Assessment (MoCA) is widely used as a brief screening measure to characterize overall cognitive status. Although only delayed free recall of the brief 5‐item memory list contributes to widely used MoCA total scores, the optional cued recall and multiple‐choice recognition subtests may provide better diagnostic accuracy than free recall alone.MethodData on 719 individuals with Mild Cognitive Impairment and 601 cognitively unimpaired controls were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The Rey Auditory Verbal Learning Test (AVLT) delayed free recall condition was used to characterize level of memory performance. Participants with demographically adjusted T‐scores of ≤ 2 SDs below the mean were classified as ‘impaired.’ Binary logistic regressions assessed if combined MoCA cued/recognition performance was a significant predictor of impaired delayed recall on the AVLT beyond the contribution of free recall and while covarying for age, education, and gender. Sensitivity, specificity, and likelihood ratio values were also examined for the MoCA free recall and combined cued/recognition scores.ResultFree recall on the MoCA was a significant predictor of delayed recall on the AVLT (b = ‐1.207, Wald χ2 (1) = 128.044, p < 0.001, OR = 0.299, 95%CI = [0.243, 0.369]. The addition of the combined MoCA cued recall/recognition conditions improved the overall model fit (χ2(1) = 30.616, p<.001) and predicted impaired AVLT recall such that for every additional word on combined MoCA cued recall/recognition, the likelihood of being in the AVLT memory impaired group decreased by 33% (b = ‐0.400, Wald χ2 (1) = 29.834, p < 0.001, OR = 0.670, 95%CI = [0. 581, 0.774]). Combined MoCA cued recall/recognition had both higher specificity and likelihood ratios in detecting AVLT memory impairment than MoCA free recall, while higher sensitivity values were present for MoCA free recall (see Table 1).ConclusionUse of combined cued/recognition memory conditions provides clinicians with improved diagnostic accuracy in detecting memory impairment. In settings where specificity in detecting memory impairment is important, administration of the MoCA free recall as well as cued recall and recognition conditions is recommended.
Assessing inflammasome activity in mouse models of Down syndrome and organotypic brain slice cultures
Authors: Farrell Clíona , Mumford Paige , Salih Dervis , Toomey Christina E. , Fisher Elizabeth , Wiseman Frances K 
Published: June 2023

AbstractBackgroundDown syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is a leading genetic cause of Alzheimer’s disease. Neuroinflammation occurs in the DS brain, with altered microglial morphology and transcriptional profiles, and upregulated proinflammatory cytokines, including IL‐1β. IL‐1β is produced by inflammasome activity. We hypothesize that IL‐1β levels are raised in the DS brain via upregulation of inflammasome activity or heightened sensitivity to inflammasome stimuli, which persists when people with DS develop AD.MethodLevels of 10 cytokines, including IL‐1β, TNFα and IL‐6 were measured (MSD) in the 3‐month hippocampus of a panel of segmental duplication mouse models of DS; Dp1Tyb, Dp2Tyb, Dp3Tyb, Dp9Tyb, Dp10Yey and Dp17Yey. These models have a duplication on one chromosome of a number of orthologues for Hsa21 genes. Organotypic brain slice cultures (OBSCs) were prepared from Dp1Tyb mice and stimulated with LPS ± nigericin, to determine if they have an altered response to inflammasome stimuli, as measured by ELISA for cytokines and IHC for IBA1 and ASC.ResultRaised IL‐1β abundance was identified in the hippocampus of the Dp1Tyb mouse, which has an additional copy of 148 mouse orthologues for Hsa21 genes. No difference in IL‐1β or other cytokines measured were identified in the Dp3Tyb, Dp9Tyb, Dp2Tyb, Dp10Yey or Dp17Yey hippocampus, which have 37, 76, 33, 31 and 19 genes in three copies respectively. LPS + nigericin treatment does not affect the secretion of IL‐1β from Dp1Tyb OHSCs compared to WT controls, nor the number of ASC specks formed.ConclusionRaised IL‐1β in the Dp1Tyb brain is a multigenic phenotype, with three‐copies of more than one gene/region of Hsa21 required to drive the phenotype. This is not due to increased sensitivity to inflammasome stimuli in Dp1Tyb OBSCs. Next, we will determine what products are raised in the Dp1Tyb brain that have the potential to increase IL‐1β production, and Dp1Tyb OBSCs will be treated with these products, E.g. Aβ. Here, we are further understanding the mechanisms of neuroinflammation in DS, which is critical in determining how AD‐DS differs from AD, and if people with DS can be included in AD research and clinical trials.
Computerized test‐retest of the Wisconsin Card Sorting Test in day‐to‐day consecutive performances in Mild Cognitive Impairment
Authors: Rosales‐Lagarde Alejandra , Rego Lourdes Cubero , Mendoza Enrique Vázquez , Martínez‐Alcalá Claudia 
Published: June 2023

AbstractBackgroundWe examined executive functions by testing cognitive flexibility, problem solving and response maintenance by means of the Wisconsin Card Sorting Test (WCST) on two consecutive days. This could render the performance gains obtained in the second assessment in Mild Cognitive Impaired (MCI) subjects, in contrast to a preserved cognitive function group (Control, CTRL group).Method17 older adults were evaluated with several tests (Fig. 1) and with the Neuropsi battery to classify them in two groups: those with three standard deviations below the mean in at least one of the cognitive functions (MCI group, n = 7) and those without this characteristic (n = 10) (Fig. 2). The WCST was delivered twice in a day‐to‐day assessment (1 subject did not repeat his session). A computerized version of the WCST was programmed using e‐prime software, v. 1, at the same time of day. The first three categories were randomly selected, and the categories were then repeated. A special keypad was designed, which included four keys for each card option. Written feedback on the screen was provided immediately.ResultANOVAs results did not show significant differences; nevertheless, the % of correct responses was almost significant within sessions in both groups (p < 0.07) and categories also showed a tendency towards significance between groups in the first session (p < 0.06) (Figs. 3, 4 & 5). Different subgroups emerged: from the first to the second session, one subgroup increased their frequency of categories (CTRL group: 50%; MCI group: 16.66%; chi2 = 16.6; df = 1, p < 0.0001); one subgroup lacked flexibility and remained the same (CTRL group: 30%; MCI group: 66.66%; chi2 = 13; df = 1, p < 0.0001), and one subgroup decreased the number of categories (CTRL group: 20%; MCI group: 16.66%; chi2 = 0.30; df = 1, p = 0.581).ConclusionIn this study, the percentage of correct responses, and the number of categories achieved may provide a more flexible profile of the execution abilities in older adults, which could be more informative for the detection of groups and so, of transitional stages from normality to cognitive impairment.
Social isolation, lifestyle and cognitive functioning in midlife and early‐late life: Implications for risk reduction of cognitive decline and dementia
Authors: Röhr Susanne , Pabst Alexander , Witte A. Veronica , Schroeter Matthias L. , Loeffler Markus , Villringer Arno , Riedel‐Heller Steffi G. 
Published: June 2023

AbstractBackgroundSocial isolation (SI) is considered a modifiable risk factor for cognitive decline and dementia, is associated with unhealthy lifestyle. We investigated independent and combined associations of SI and lifestyle with cognitive functioning (CF) in a midlife to early‐late life population without dementia. This informs developing more targeted preventive strategies against cognitive decline and dementia.MethodThe “LIfestyle for BRAin health” (LIBRA) score was computed for 6,203 baseline participants of the LIFE‐Adult‐Study, a population‐based German cohort. LIBRA is validated for dementia prediction in midlife to early‐late life populations, consisting of 12 modifiable factors (heart disease, kidney disease, diabetes, obesity, hypertension, hypercholesterolemia, alcohol consumption, smoking, physical inactivity, diet, depression, cognitive activity). Higher scores (‐5.9,+12.7) indicate “worse” lifestyle. SI was assessed with the short Lubben Social Network Scale (score < 12). For CF, we calculated a z‐standardized composite score of the Verbal Fluency Test, the Trail Making Test A and B. Associations of SI and LIBRA with CF were investigated using generalized linear modelling. Bootstrapped structural equation modelling (SEM) tested whether LIBRA mediated the association between SI and CF. Sampling weights were applied, variables z‐standardized for SEM.ResultsParticipants were M = 57.7 (SD = 12.0, range: 40‐79) years old; 50.7% were female; 15.8% were socially isolated. SI (β: ‐.17, 95%CI[‐.24,‐.10]; Wald = 21.45, p < .001) and a higher LIBRA score (β: ‐.03, 95%CI[‐.04,‐.02]; Wald = 31.49, p < .001) were independently associated with lower CF; there was no interaction (β: ‐.003, 95%CI[‐.03,.02]; Wald = 0.06, p = .814; Fig.1). Bootstrapped SEM (reps = 10,000; R² = .34) indicated that LIBRA partially mediated the association between SI and CF (IE = ‐.006, 95%CI[‐.008,‐.003], p < .001; proportion mediated = 8.5%; Fig.2).ConclusionCF is lower in socially isolated than socially integrated individuals without dementia. The CF difference can be partially attributed to modifiable health and lifestyle factors; however, only to a small extent. Therefore, public health initiatives aiming at preventing SI might be more effective in promoting good CF than lifestyle interventions in socially isolated individuals in midlife to early‐late life. This would likely benefit risk reduction of cognitive decline and dementia in later life.
Dual Role of Low Frequency Magnetic Field on Neuroinflammation Induced Dendritic Trimming And Memory Impairment on Rat Model of Sporadic Alzheimer’s Disease
Authors: Roy Avishek , Sharma Binney , Iyenger Soumya , Gupta Yogendra Kumar , Jain Suman , Banerjee Jyotirmoy 
Published: June 2023

AbstractBackgroundGliosis and dendritic loss is reported to be secondary to the amyloid beta (Aß) and hyperphosphorylated tau (hp‐tau) production in Alzheimer’s disease(AD) brain. STZ administration is reported to induce sporadic AD. Previous clinical or preclinical studies on effect of rTMS treatment in AD patients or APP23 mice showed cognitive improvement alone or as adjuvant therapy along‐with amelioration of the glial aggravation in the hippocampus. However, studies on the effect of magnetic field stimulation on the gliosis related dendritic trimming in animal models of sporadic AD is elusive. Therefore, in the present study we have looked in to the effect of extremely low frequency magnetic field stimulation (ELF‐MF; 17.96µT, 50Hz, 2hr/day) for one month post‐injection of STZ (bilateral, 3mg/kg).MethodTotal 45 animals were (ethical no. 937/IAEC/2016) randomly divided into five groups: Control, Sham, AD, Sham+MF and AD+MF. After assessing retention of spatial and avoidance memory using Morris water maze and passive avoidance step down test on 30th day, animals were sacrificed and tissues processed for oxidative stress and immunofluorescence, Golgi‐Cox staining.ResultBehavioural analysis revealed spatial memory improvement with no effect on the avoidance memory loss in AD+MF group as compared to AD group. We also found significant decrease in superoxide dismutase, catalase, GSH and increase in malon‐di‐aldehyde (MDA) in AD group. ELF‐MF treatment only reduced MDA level in hippocampus and frontal cortex. GFAP, IBA‐1 and hp‐tau (ser356) positive cells were found to be reduced in AD+MF group, as compared to all groups except Control. Sholl analysis revealed partial improvement of reduction in the number of intersection, bifurcation and length in basal and apical dendrite in the AD group after ELF‐MF treatment in CA3 layer. Convex hull analysis revealed a contradictory result showing reduction in apical (p = 0.018) and increase in basal dendrite (p = 0.038) of AD group as compared to control.ConclusionThese findings suggests dual role of ELF‐MF exposure on STZ model of AD showing improvement of spatial memory by reducing the gliosis induced dendritic loss but loss in avoidance memory.
Inhibition of Fli‐1 attenuates inflammation, pericyte loss and cognitive deficits in Alzheimer’s disease
Authors: Li Pengfei , Wu Yan , Hamlett Eric D , Goodwin Andrew , Halushka Perry , Carroll Steven , Liu Meng , Fan Hongkuan 
Published: June 2023

AbstractBackgroundBrain pericytes maintain the integrity of the blood‐brain barrier (BBB) and facilitate the removal of amyloid β (Aβ) which is critical to healthy brain activity (Ethan et al., Brain Pathol., 24: 371‐386, 2014). Pericyte degeneration has been observed in brains from patients with Alzheimer’s disease (AD) and animal models (Jesse et al., Brain Pathol., 23: 303‐10, 2013; Wu et al., Aging (Albany NY), 11: 6120‐6133, 2019). Our previous data demonstrated that friend leukemia virus integration 1 (Fli‐1), an ETS transcription factor, regulates pericyte viability and vascular injury in murine sepsis (Li et al., J Infect Dis, 218: 1995‐2005, 2018); however, the role of Fli‐1 in AD remains unknown.MethodsFli‐1 levels and pericyte number were detected in postmortem brains from 21 patients with AD and 17 healthy controls, and in 5xFAD transgenic mice. Control or Fli‐1 antisense oligonucleotide Gapmers were injected into the hippocampus of 5xFAD mice at 3 and 4.5 months of age. Pericyte number, inflammatory mediators, Aβ deposition, BBB function and cognitive deficits were evaluated at 6 months of age. Human brain pericytes were transfected with control or Fli‐1 antisense Gapmers for 48 h and cultured with or without freshly aggregated Aβ40 for 7 consecutive days. Cell viability and apoptosis were detected.ResultsWe demonstrated that Fli‐1 expression was increased in postmortem brains from a cohort of human AD donors and in 5xFAD mice, which corresponded with a decreased pericyte number, elevated inflammatory mediators, and increased Aβ accumulation as compared to cognitively normal individuals and WT mice, respectively. Antisense oligonucleotide Fli‐1 Gapmer administrated via intrahippocampal injection decelerated pericyte loss, reduced inflammatory responses, ameliorated cognitive deficits, improved BBB dysfunction, and decreased Aβ deposition in 5xFAD mice. Fli‐1 Gapmer‐mediated inhibition of Fli‐1 protected against Aβ accumulation induced human brain pericyte apoptosis in vitro.ConclusionThese composite results indicate that Fli‐1 contributes to pericyte loss, inflammatory response, Aβ deposition, vascular dysfunction and cognitive decline, and suggest that suppression of Fli‐1 may represent a novel therapeutic strategy for AD.
Assessment of motivation, readiness to change, and general wellbeing among participants enrolled in a longitudinal study on brain health self‐management
Authors: Jose Roslin , Ross Sarah E 
Published: June 2023

AbstractBackgroundLifestyle choices are modifiable factors that contribute to the onset Alzheimer’s disease and related dementias. Health coaching can address risk factors related to lifestyle choices. This study aims to explore trends in motivation to change and the general health of participants enrolled in a brain health self‐management program.MethodThe program uses health coaching, education, and targeted assessments to provide a personalized approach for facilitating brain healthy lifestyle changes. After program enrollment, participants complete assessments specific to the 7 pillars of brain health (Diet, Exercise, Social Engagement, Cognitive Activity, Sleep, Mindfulness & Outlook, and General Health), demographics, and a motivation to change assessment. Participants then attend an intake visit and virtual health coaching sessions. Health coaching focuses on helping participants create specific lifestyle goal(s) in their pillar(s) of interest. We used the Motivation to Change Lifestyle and Health Behaviour for Dementia Risk Reduction (MCLHB‐DRR) Scale to assess for motivation to change, Readiness ruler from the Permanente Medical Group, and the SF‐20 questionnaire to assess General Health. We assessed for trends in participant demographics, motivation, readiness, and general wellbeing.ResultAs of January 2022, 40 participants enrolled for the study, 36 completed the pre‐survey, and 25 attended the intake and the virtual health coaching visits to set one or more brain healthy lifestyle goal. The participant demographics were predominantly female (80%), Caucasian (91.67%), and non‐Hispanic (97.22%), with an average participant age of 76.6. Among the components of the MCLHB‐DRR scale based on the Health Belief Model, the participants overall had a high average Self‐Efficacy 8.2±1.7 (4‐10) and General Health Motivation 17.5±2.7 (5‐20). The average readiness to work on the goal(s) set was 8.24±1.7 on a scale of 0‐10 (0‐Not Ready; 10‐Ready), with Exercise goals being the highest (9.2±0.8), and social engagement the lowest (5.7±2.8). 44.4% of participants rated their health as good (3 on scale 1‐5).ConclusionThis program intends to promote life‐style changes aimed at dementia risk reduction and improving overall brain health. Those who elected to participate where highly motivated to implement lifestyle improvements and reported high ratings of their perception of their overall health.