bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems biologic analysis of inverse etiological mechanism between Alzheimer’s disease and cancer identified key astrocytic signaling pathways in restraining Alzheimer’s disease pathogenesis
Authors: Zhao Hong , Vasquez Matthew , Ahn Ju Young , Sheng Jianting , Yin Zheng , Wong Stephen T.C. 
Published: December 2023

AbstractBackgroundA 35% lower incidence of Alzheimer’s disease (AD) among older cancer survivors was reported versus those without cancer history(Ma, Yu et al. 2014, Zhang, Guo et al. 2015, Bowles, Walker et al. 2017, Ospina‐Romero, Abdiwahab et al. 2019, Ospina‐Romero, Glymour et al. 2020). The exclusive cellular and molecular mechanism between these two diseases may open up new vista in discovering novel mechanisms of action and effective therapeutic strategies for AD.MethodA breast cancer‐in‐AD mouse model was established by injecting a very low number of AT3 murine breast cancer cells (1×104) into the left cardiac ventricle of 1‐month‐old female 5xFAD mice (Tg6799 on a congenic C57BL6 background, n = 5). Mice were sacrificed four weeks after tumor injection. Their brains were processed for amyloid plaque, astrocyte, microglia and oligodendrocyte immunostaining and isolation of astrocytes and microglia for generating cell‐specific RNA sequencing data, which were analyzed and then modeled by the CCCExplorer software(Choi, Sheng et al. 2015, Tsz‐Lun Yeung 2019) to identify multi‐cellular crosstalk signaling in association with plaque burden.ResultIn the breast cancer‐in‐AD mouse model, we identified a significant reduction (45%) of Aβ plaque burden in the brain of tumor‐bearing AD mice in comparing to the age‐matched cancer‐free AD mice (Fig. 1). We observed an 35% increase of the total astrocyte area and 50% increase of plaque‐associated astrocytes in the tumor‐bearing AD mice (Fig. 2). Our systems biologic analysis indicated the elevated expressions of about 50 marker genes for reactive astrocytes and positive regulators of astrocyte reactivity; suppression of Aβ production but increase of Aβ clearance in astrocytes of tumor‐bearing AD mice, and identification of 1,729 differentially expressed genes (DEGs) including 46 receptors, 45 ligands, and 12 signaling pathways of astrocytes in mediating an active astrocyte‐microglia interaction in synergistically regulating Aβ homeostasis (Fig. 3).ConclusionAmyloid burden is significantly reduced in AD mice bearing tumors, predominantly associated with astrocyte activation. The AD protective astrocyte signaling is being investigated for repositioning known drugs targeting early AD.
Association of mood disorder and bone health with cognitive function among healthy ageing men
Authors: Mehta Kanika , Mohebbi Mohammadreza , Pasco Julie A , Williams Lana J , Walder Ken , Ng Boon , Gupta Veer Bala 
Published: December 2023

AbstractBackgroundHigh dementia prevalence and associated disability have necessitated a focus on the identification of potentially modifiable risk factors. Mental and physical health conditions such as mood disorder and bone loss have been previously linked with poor cognition although their combined effect remains largely unknown.1 We investigated whether an interaction between mood disorder and bone loss is associated with cognitive function in a population‐based sample of men.MethodParticipants free from severe cognitive impairment were drawn from the Geelong Osteoporosis Study (n = 442, mean age = 63.5 years) and cognition was assessed via the CogState Brief Battery that measured performance across four domains (psychomotor function, attention, learning and working memory).2 Mood disorder and hip bone mineral density (BMD) were evaluated using a semi‐structured clinical interview and dual‐energy x‐ray absorptiometry, respectively. Linear regression analyses adjusted for age, education, SES, mobility, smoking status, alcohol consumption and APOE ε4 status were conducted to investigate whether lifetime history of a mood disorder, hip BMD or two‐way interaction are associated with overall cognitive function and cognitive performance in individual domains.ResultHip BMD (Bcoeff 0.56 95% CI 0.07, 1.05) but not mood disorder (Bcoeff ‐0.50 95% CI ‐0.20, 0.10) was associated with overall cognitive function after accounting for potential confounders. Significant interaction effects were observed between the two exposures (Bcoeff ‐1.37 95% CI ‐2.49, ‐0.26) suggesting that individuals without a mood disorder displayed better overall cognitive performance with increasing BMD, whereas those with a lifetime history of mood disorder displayed poorer cognitive function with increasing BMD. Interaction effects were also observed for the individual cognitive domains (Fig. 1). Results remained virtually unchanged when mood disorder was limited to major depressive disorder.ConclusionThis is the first‐ever study that reported an interaction between mood disorder and BMD that could be accounted for in establishing risk factors for cognitive decline.1. Mehta K, Thandavan SP, Mohebbi M, Pasco JA, Williams LJ, Walder K, et al. Depression and bone loss as risk factors for cognitive decline: A systematic review and meta‐analysis. Ageing Res Rev 2022; 76: 101575.2. Pasco JA, Nicholson GC, Kotowicz MA. Cohort profile: Geelong Osteoporosis Study. Int J Epidemiol 2012; 41: 1565‐75.
Effect of increasing participation in habitual intellectual activities on cognitive function in older adults without clinical dementia ‐ update on the findings of a randomized controlled trial
Authors: Lee Allen TC 
Published: December 2023

AbstractBackgroundThe preliminary findings of our randomized controlled trial, which aims to test whether doubling calligraphy practice leads to more cognitive benefits in older adults without clinical dementia, were presented in AAIC 2022. With the data collection near completion, we will present the latest findings of our study in AAIC 2023.MethodA total of 112 community‐living older adults without clinical dementia and with prior practice of calligraphy were recruited and randomly allocated into either the control group where they continued their usual practice of calligraphy or the intervention group where they doubled their practice. Comprehensive standardized cognitive assessments were performed before and after the 6‐month intervention.ResultChanges in global cognition and individual cognitive domains will be compared between the intervention and control groups. Compliance of intervention will also be reviewed.ConclusionOur findings will add insight to the effect of increasing the “dosage” of intellectual activities on cognitive function and the acceptability of cognitive intervention among community‐living older adults at risk of dementia.
MicroRNA expression based on toxic Oligomeric Amyloid Beta and Burden of Cerebrovascular Disease
Authors: Sandhu Gurveen Kaur , Zailan Fatin Zahra , Vipin Ashwati , Soo See Ann , Kumar Dilip , Leow Yi Jin , Koh Chen Ling , Chen James Xiao Yuan , Lee Faith Phemie Hui En , Ghildiyal Smriti , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundMicroRNAs(miRNAs) form the most intensively characterised branch of non‐coding RNAs, with universal expression in a repertoire of biofluids and active regulatory roles in multiple biological pathways(Blount, Coursey, and Kocerha 2022). Therefore, any perturbance in miRNA expression produces pronounced biological effects, due to its pleiotropic nature(Blount, Coursey, and Kocerha 2022). A variety of miRNAs have been investigated in multiple dementia syndromes (Blount, Coursey, and Kocerha 2022). However, what remains to be evaluated is differential miRNA expression in dementia classified using the more toxic oligomeric amyloid beta(OAβ) as well as based on burden of cerebrovascular disease(CVD).MethodA cross‐sectional pilot study was conducted in a cohort of 24 research participants(Table 1), stratified on the basis of their plasma OAβ levels [Multimer Detection System based plasma OAβ analysis(PeopleBio Inc, South Korea)](Dominguez et al. 2022). T3 ‐ based MRI data was evaluated for CVD status ‐ White Matter Hyperintensity load, was scored using the Fazekas scale(Table 1). Blood plasma‐based expression profiling of 376 miRNAs was conducted using the ID3EAL™ PanoramiR miRNA Knowledge Panel(MiRXES Pte Ltd, Singapore) and normalised miRNA expression was defined via the delta‐delta(d) Ct method. MiRNA target interaction analyses was conducted using miRTarBase 9.0, revealing potential reactome pathways of interest(Huang et al. 2022).ResultMean age and MoCA scores are 60.05 and 25.42 respectively (Table 1). 10 miRNAs(upregulated : hsa‐miR‐42, hsa‐miR‐378c, hsa‐miR‐938; downregulated: hsa‐miR‐545‐3p, hsa‐miR‐449c‐5p, hsa‐miR‐657, hsa‐miR‐23c, hsa‐miR‐888‐5p, hsa‐miR‐599, hsa‐let‐7d‐5p) were significantly differentially expressed in OAβ positivity(Table 2). 6 miRNAs(upregulated: hsa‐miR‐513c‐5p, hsa‐miR‐592; downregulated: hsa‐miR‐98‐5p, hsa‐miR‐744‐5p, hsa‐let‐7d‐5p, hsa‐miR‐517‐5p were significantly differentially expressed in CVD(Table 2). Reactome pathways demonstrating putative biological relevance are the FOXO/p53 mediated transcriptional regulation (metabolism/senescence/neuronal genes),Caspase mediated inflammatory activation, Insulin/IGF‐1/PI3K/Akt/GSK3β mediated metabolic signalling, IL‐4/IL‐13 mediated immune(inflammatory) signalling, Nervous System/Axonal Development and WNT Signalling(Table 2).ConclusionFindings from this cross‐sectional pilot study, have revealed 16 miRNAs to be promising biomarker candidates within the OAβ positivity and CVD burden setting. Longitudinal study with larger sample size is on‐going to confirm and validate these findings.The authors wish to express their sincere gratitude to MiRXES Pte Ltd for their technical expertise and efforts towards the miRNA expression profiling and associated analyses.
Interleukin‐3 is associated with soluble TREM2 and mediates amyloid and tau pathology in Alzheimer’s disease
Authors: Wang Zhi‐Bo , Ma Ya‐Hui , Sun Yan , Tan Lan , Wang Hui‐Fu , Yu Jin‐Tai ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2023

AbstractBackgroundDysfunction of glial cell communication is involved in Alzheimer’s disease (AD) pathogenesis. Recent studies reported that interleukin‐3 (IL‐3) participated in astrocyte‐microglia crosstalk and restricted pathological progression in AD mice. However, how IL‐3 relates to microglial activity and AD pathology in humans remains unclear.MethodWe included 311 participants with cerebrospinal fluid (CSF) IL‐3, sTREM2 (microglial biomarker), and AD biomarkers (Aβ42, p‐tau, and t‐tau) from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We compared IL‐3 levels in different stages of AD and assessed the associations between IL‐3 with sTREM2 and AD biomarkers at baseline and with longitudinal cognitive change. Mediation models were used to explore the potential mechanism of how IL‐3 affects sTREM2 and AD pathology.ResultCSF IL‐3 levels decreased with increasing Aβ pathology and increased with increasing tau pathology, especially in cognitive impairment participants (Figure 1). CSF IL‐3 was significantly associated with CSF sTREM2 and CSF AD biomarkers (Figure 2). Mediation analysis showed that IL‐3 and sTREM2 mediated the effects of CSF Aβ on CSF tau pathology (βp‐tau = 0.053, βt‐tau = 0.055, all p < 0.001) (Figure 3).ConclusionOur findings suggest that IL‐3 is associated with the microglia biomarker and that they respond strongly to amyloid and tau pathologies. Hence, IL‐3 could be a key marker for clinical trial design. We encourage future studies on enhancing IL‐3 levels as a therapeutic intervention to slow the development of AD pathology.
Proteomic analysis reveal early differences in plasma exosomes of Aβ(+) vs Aβ(‐) patients with early‐onset mild cognitive impairment: from BIOFACE to BIOPEXAL study
Authors: Cano Amanda , De Antonio Ester Esteban‐ , Bernuz Mireia , Puerta Raquel , García‐González Pablo , de Rojas Itziar , Olivé Clàudia , Pérez‐Cordón Alba , Montrreal Laura , Núñez‐Llaves Raúl , Sotolongo‐Grau Oscar , Valero Sergi , Alegret Montserrat , Martín Elvira , Adami Pamela V Martino , Arriola Miren Ettcheto , Camins Antonio , Vivas Assumpta , Chiari Marta Gómez , Orellana Adelina , Tárraga Lluís , Marquié Marta , Ramirez Alfredo , Martí Mercè , Pividori Maria Isable , Boada Mercè , Ruiz Agustin 
Published: December 2023

AbstractBackgroundin the clinical course of Alzheimer’s disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p‐tau‐mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre‐screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma exosomes (pEXOs) are gaining popularity as a new source of biomarkers for the early stages of AD developmentMethodto identify an exosome proteomics signature linked to prodromal AD, we performed a cross‐sectional study on two groups of patients with early‐onset MCI (EOMCI) (Aβ +/‐) in which 184 biomarkers were measured in pEXOs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink© proteomics.Resultthe obtained results showed that proteins measured in pEXOs from EOMCI patients with established amyloidosis correlated with CSF p‐tau181 levels, brain ventricle volume changes, white matter hyperintensities, and MMSE scores. In addition, the correlations of pEXOs proteins with different parameters were able to discriminate between EOMCI Aβ(+) and Aβ(‐) patients, whereas the CSF or plasma proteome did not.Conclusionour findings suggest that pEXOs could be able to provide information regarding the initial amyloidotic changes of AD. At this early stage, our results may indicate that pEXOs biomarker profile is associated with the AD‐specific neurodegeneration process governed by p‐tau and Aβ. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development. However, additional research is required to comprehend the molecular pathways underlying these findings and validate the obtained results in an independent cohort.
Wireless Dosage Monitoring for Donepezil Transdermal Patches as a Novel Concept
Authors: Bendas Ehab R 
Published: December 2023

AbstractRemote therapy, also known as teletherapy or online therapy, refers to the provision of mental health services through electronic means, such as phone, text, or video conferencing. With the advent of the internet and other digital technologies, it has become increasingly possible for therapists and patients to interact remotely, without the need for in‐person visits.Remote therapy has gained popularity in recent years, particularly during the COVID‐19 pandemic, as it allows individuals to access mental health support from the safety and convenience of their own homes. It is also a useful option for those who live in rural or underserved areas, where access to in‐person therapy may be limited.Donepezil (cholinesterase inhibitor) is effective for improving the cognitive and global functioning of patients with Alzheimer’s disease. This drug was formulated as transdermal patch by the ethanol based nano carrier & micro gas sensor. Our work intends to create a simple approach to administer Donepezil systemically by applying a transdermal patch, as well as a practical monitoring technique by employing a gas sensor that collects data and wirelessly transmits it to cell phone application. The application depends on short massage services. Wireless technology offers several advantages, including improved data mobility and data transfer via various methods such as Wi‐Fi, internet connection, or Bluetooth to enable continuous medical monitoring. The sensor has the advantages of being small, not battery operated and delivering doses without human interference that reduces error, making the technique favorable for elderly and mentally disabled patients. This innovative technology permits the physician to monitor the drug level in the patch and give an alarm for applying the next doses through cell phone application.In conclusion, remote therapy using the transdermal route of administration is a valuable option for individuals suffering from cognitive disease like Alzheimer’s Disease because it avoids first‐pass effects, reduces adverse symptoms associated with the oral route, and increases the economic benefits of using the correct doses when needed.
Prognostic value of Neurofilament light chain, [18F]‐PI2620 PET and [18F]GE‐180‐PET in amyloid‐negative Corticobasal Syndrome
Authors: Palleis Carla , Franzmeier Nicolai , Weidinger Endy , Bernhardt Alexander , Katzdobler Sabrina , Finze Anika , Nuscher Brigitte , Rauchmann Boris‐Stephan , Perneczky Robert , Haass Christian , Brendel Matthias , Levin Johannes , Höglinger Günter 
Published: December 2023

AbstractBackgroundCorticobasal syndrome (CBS) with underlying 4‐repeat tauopathy is a progressive neurodegenerative disorder characterized by declining cognitive and motor functions. Biomarkers for assessing pathological brain changes in CBS including tau‐ and microglia‐PET or neurofilament light chain (NfL) have recently been evaluated for differential diagnosis and disease staging, yet the prognostic accuracy of these biomarkers for predicting disease trajectories remains unclear. To address this, we performed a head‐to‐head comparison of neuroimaging (tau‐PET, microglia‐PET) and plasma biomarker NfL as prognostic tools for future clinical trajectories in 21 CBS patients with longitudinal clinical data.MethodWe included 21 clinically diagnosed CBS patients with ∼2‐year clinical follow‐up data who underwent baseline [18F]PI‐2620‐PET for assessing tau pathology, [18F]GE‐180‐PET for microglia activation and plasma‐NfL for neurodegeneration. All patients were negative on amyloid biomarkers. To quantify tau and microglia load we assessed summary scores of whole‐brain, cortical and subcortical tracer signal. NfL was assessed using immunoassays on the Simoa platform. Symptom progression was determined using a battery of cognitive and motor tests. Using linear mixed models, we tested whether the assessed biomarkers at baseline were associated with faster progression of symptoms over time (i.e. time x biomarker interaction).ResultOverall, there was on average a rapid decline over time on the assessed clinical scores. For tau‐PET, CBS patients with higher global tau load showed faster clinical progression. This time x tau‐PET interaction was driven by cortical rather than subcortical tau‐PET load. Patients with higher [18F]GE‐180‐PET whole‐brain load showed slower clinical progression. Concerning plasma biomarker NfL, higher plasma‐NfL was prognostic of faster clinical deterioration. In a subsequent sensitivity analysis, we found that tau‐PET, microglia‐PET as well as plasma‐NfL showed significant (i.e. p<0.05) interaction effects with time on clinical trajectories when tested in the same model, suggesting that these biomarkers explain unique variability in future disease trajectories.Conclusion[18F]PI‐2620 tau‐PET, [18F]GE‐180 microglia‐PET and plasma‐NfL show prognostic potential for clinical progression in CBS patients with probable 4‐repeat tauopathy, which can be useful for clinical decision making as well as stratifying patients in clinical trials.
Spectrum of Neuropsychiatric Symptoms in Southeast Asians with Prodromal Dementia
Authors: Leow Yi Jin , Soo See Ann , Kumar Dilip , Vipin Ashwati , Zailan Fatin Zahra , Sandhu Gurveen Kaur , Lee Faith Phemie Hui En , Ghildiyal Smriti , Chen James Xiao Yuan , Dang Chao , Ng Kok Pin , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundBehavioral and psychological symptoms are one of the earliest observable changes when a person experiences cognitive decline. These symptoms are common and are known as Neuropsychiatric symptoms(NPS), which increases risk of progression to dementia. The prevalence of NPS was compared in a cohort of Southeast Asian adults with Subjective Cognitive Decline(SCD) and Mild Cognitive Impairment(MCI).MethodThis study utilized cross‐sectional data from the Biomarkers and Cognition Study, Singapore(BIOCIS). From February to December 2022, participants who met criteria for SCD and MCI in accordance with NIA‐AA’s criteria were classified into two groups, NPS and without‐NPS, based on clinical cut‐offs of Depression Anxiety Stress Scales(DASS) scores. Self‐reported questionnaires assessed behavioral symptoms ‐ Mild Behavioral Impairment‐Checklist(MBI‐C); Dementia‐Quality of Life Instrument(Dem‐QOL); International Physical Activity Questionnaire(IPAQ); and Pittsburgh Sleep Quality Index(PSQI). Group comparisons of data were applied separately using univariate analyses. A Receiver Operating Characteristic analysis was conducted to test the diagnostic performance of MBI‐C total, MBI‐C‐subdomains, and PSQI in distinguishing participants with NPS and without‐NPS.Result488 participants (μ age = 62.7±9.64,42.2% males) were analyzed. 133(27.25%) reported significant NPS symptoms. Participants with NPS reported significantly more symptoms on MBI‐C‐total(p<.001); interest(p<.001); mood(p<.001); control(p<.001), social(p<.001), and beliefs(p<.001) subdomains; poorer sleep(p<.001) and lower quality of life(p<.001) compared to participants without‐NPS(Table 1). MBI‐C‐total, MBI‐C‐mood and MBI‐C‐control subdomains were effective in discriminating between participants with and without NPS, with an acceptable Area Under the Curve: .782(.732‐.833) for MBI‐C‐total, .753(.699‐.807) for MBI‐C‐mood, and .753(.699‐.807) for MBI‐C‐control(Figure 1 and Table 2).ConclusionIn a prodromal cohort of southeast Asians, participants with NPS reported significantly worse scores on MBI‐C‐total and subdomains, specifically ‐ decreased motivation, emotional dysregulation, impulse control, social inappropriateness, abnormal perceptions, as well as poorer sleep quality and a lower quality of life compared to participants without‐NPS. The results are keeping with the strong evidence that behavioral changes are among the first symptoms noticeable to the person themselves as they begin to experience cognitive decline. The self‐reported questionnaires used are easily administered and brief, which has important real‐world relevance for early diagnoses of, and timely intervention for prodromal dementia. Further studies of BIOCIS is on‐going to investigate the impact of NPS on cognitive decline.