Alzheimer's Disease Disorders Research Articles

Down regulation of the c-Fos/MAP kinase signaling pathway during learning memory processes coincides with low GnRH levels in aluminum chloride-induced Alzheimer's male rats.

Aluminum chloride (Al) is associated with Alzheimer's disease (AD) and reproductive disorders. But the relationship between gonadotropin-releasing hormone (GnRH) and c-Fos levels, the end product of MAP-kinase signaling, in AD is unknown, so we aimed to investigate this relationship. We exposed rats to Al dissolved in drinking water (10 and 50mg/kg) for two and four weeks. The control group received only drinking water. At the end, the blood sample was collected under deep anesthesia and the brain was dissected on ice, and the testicular tissue was fixed in formalin. Amyloid beta (βA) plaques in brain regions and the number of CA1 neurons were evaluated by Congo red staining and cresyl violet staining. Activation of neuronal nitric oxide synthase (nNOS) was studied using NADPH-diaphorase. The levels of c-Fos and testosterone receptors in the target area were examined immunohistochemically. Brain GnRH levels were determined by blotting, and serum levels of gonadotropins and steroids were measured by enzyme-linked immunosorbent assay (ELISA). All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. The accumulation of βA plaque was observed along with a decrease in the number of CA1 pyramidal neurons and a significant decrease in the levels of c-Fos and GnRH in the brains of rats receiving Al, which was aligned with a significant decrease in serum levels of testosterone and LH. This study, for the first time, showed a link between dementia and a concomitant decrease in brain GnRH and c-Fos levels.

Orexin Receptor Antagonists for the Prevention and Treatment of Alzheimer's Disease and Associated Sleep Disorders.

Orexins/hypocretins are neuropeptides produced by the hypothalamic neurons, binding two G-protein coupled receptors (orexin 1 and orexin 2 receptors) and playing a critical role in regulating arousal, wakefulness, and various physiological functions. Given the high prevalence of sleep disturbances in Alzheimer's disease (AD) and their reported involvement in AD pathophysiology, the orexin system is hypothesized to contribute to the disease pathogenesis. Specifically, recent evidence suggests that orexin's influence may extend beyond sleep regulation, potentially affecting amyloid-β and tau pathologies. Dual orexin receptor antagonists (DORAs), namely suvorexant, lemborexant, and daridorexant, demonstrated efficacy in treating chronic insomnia disorder across diverse clinical populations. Considering their stabilizing effects on sleep parameters and emerging evidence of a possible neuroprotective role, these agents represent a promising strategy for AD management. This leading article reviews the potential use of orexin receptor antagonists in AD, particularly focusing on their effect in modulating disease-associated sleep disturbances and clinical outcomes. Overall, clinical studies support the use of DORAs to enhance sleep quality in patients with AD with comorbid sleep and circadian sleep-wake rhythm disorders. Preliminary results also suggest that these compounds might influence AD pathology, potentially affecting disease progression. Conversely, research on selective orexin receptor antagonists in AD is currently limited. Further investigation is needed to explore orexin antagonism not only as a symptomatic treatment for sleep disturbances, but also for its broader implications in modifying AD neurodegeneration, emphasizing mechanisms of action and long-term outcomes.

Comprehensive EEG Signal Feature Extraction for Neurological Disorder Diagnosis: Focus on Alzheimer's, Parkinson's, and Seizure Disorders

This research paper examines the use of Electroencephalogram (EEG) signal feature extraction for diagnosing neurological disorders, specifically Alzheimer's, Parkinson's, and seizure disorders. It evaluates various methods for categorizing EEG signals, including time-domain, frequency-domain, and statistical transformations emphasizing their effectiveness in distinguishing relevant brainwave patterns (beta, alpha, theta, delta) from artifacts like eye blinks and muscle movements. The study highlights the challenges in artifact removal and provides an overview of key feature extraction techniques, particularly in the time and frequency domains. The implementation section details the application of machine learning algorithms to classify mental states using statistical features from EEG signals. The research identifies specific EEG patterns associated with Alzheimer's, Parkinson's, and seizure disorders, noting alterations in alpha, theta, and delta waves. The paper underscores the critical role of EEG feature extraction in diagnosing neurological disorders and recommends incorporating additional frequency-based methods to enhance predictive accuracy in future research.

Medical Foods for the management of Chronic Illness and their Regulations in India, US and European Union

As many chronic illnesses are incurable and require repeated treatments, this problem contributes to long-term drug use. But when it comes to managing and treating chronic illnesses, medical foods can provide an alternative to natural medications. Medical foods are foods that have been particularly prepared to meet the unique dietary needs of people with specific illnesses. When it comes to therapeutic applications such as deglutition, dyspepsia, or eating disorders, they are crucial in providing patients with nutritional support. In addition, they significantly improve patients' quality of life by lowering drug use, averting problems that could result from an excessive reliance on pharmaceuticals, and saving treatment costs. Depending on the illness, medical foods' nutritional content can be adjusted and customized. They are exempt from laws pertaining to drugs since they are not drugs. Every medical food is created especially for the chronic condition in question. As a result, the purpose of this review is to clarify the use of medical foods for conditions such as Parkinson's, Alzheimer's, anxiety and sleep disorders, pain syndrome, cancer, congenital metabolic disorders, and diabetes mellitus, and to suggest their use as a dietary supplement for these long-term illnesses.

N-BodyPat: Investigation on the dementia and Alzheimer's disorder detection using EEG signals

The N-body problem is a remarkable research topic in physics. We propose a new feature extraction model inspired by the N-body trajectory and test its feature extraction capability. In the first part of the research, an open-access electroencephalogram (EEG) dataset is used to test the proposed method. This dataset has three classes, namely (i) Alzheimer's Disorder (AD), (ii) frontal dementia (FD), and (iii) control groups. In the second step of the study, the EEG signals were divided into segments of 15 s in length, which resulted in 4,661 EEG signals. In the third part of the study, the proposed new self-organized feature engineering (SOFE) model is used to classify the EEG signals automatically. For this SOFE, two novel methods were presented: (i) a dynamic feature extraction function using a graph of the N-Body orbital, termed N-BodyPat, and (ii) an attention pooling function. A multileveled and combinational feature extraction method was proposed by deploying both methods. A feature selection function using ReliefF and Neighborhood Component Analysis (RFNCA) was used to choose the most informative features. An ensemble k-nearest neighbors (EkNN) classifier was employed in the classification phase. Our proposed N-BodyPat generates seven feature vectors for each channel, and the utilized EEG signal dataset contains 19 channels. In this aspect,133 (=19 × 7) EkNN-based outcomes were created. To attain higher classification performance by employing these 133 EkNN-based outcomes, an iterative majority voting (IMV)-based information fusion method was applied, and the most accurate outcomes were selected automatically. The recommended N-BodyPat-based SOFE achieved a classification accuracy of 99.64 %.

Feasibility of Using Simulation to Evaluate Implementation Fidelity in an Advance Care Planning Pragmatic Trial.

Background and Objectives: Traditional methods of fidelity monitoring are not possible in pragmatic trials in real-world clinical settings. We describe our approach to monitoring and reinforcing the fidelity to ACP conversations for a hard-to-reach subpopulation by using standardized patients in a pragmatic trial. Research Design and Methods: We developed standardized patient scenarios grounded in the Respecting Choices First Steps™ Advance Care Planning curriculum to provide an opportunity to reinforce and assess ACP facilitator competency. Scenarios represented one-on-one encounters. The first case was a standardized patient with cognitive impairment and the second case involved a standardized patient with dementia and their care partner. A previously validated fidelity checklist was used to score skills and behaviors observed during simulations including encounter set-up, ACP topics, and general communication. Simulations involved voice teleconferencing to align primary modality of ACP in the pragmatic trial. Results: Six facilitators completed two standardized patient cases each. Overall fidelity scores were moderately high (78.8% ± 11.7; 63.4 - 95.6) for the case with cognitive impairment and for the case with the patient with dementia and care partner (76.2% ± 13.0; 54.4 - 91.5). Discussion and Implications: Simulation using standardized patients supported fidelity monitoring and provided coachable feedback to support facilitator competency. Our study can help inform future research and training related to advance care planning in older adults living with Alzheimer's disease and related disorders.

The impact of social isolation and loneliness on the well-being of carers of a person with dementia in aotearoa New Zealand.

Dementia is a leading cause of disability, and as the population ages, there will be a greater need for friends and family to care for people with Dementia. Unfortunately, informal care for a person with dementia is associated with poor psychological and physical health and lower quality of life of the caregiver. The aim of the present study was to understand how to best support caregivers within their communities by examining their experience of loneliness, isolation, and their relationship with well-being. The study used a representative sample of the New Zealand population in terms of ethnicity, age, gender, education, and income and asked people if they were a primary caregiver of a person with Alzheimer's Disease or related disorder. Both loneliness and isolation were linked to overall well-being; however, loneliness was a stronger predictor of satisfaction with relationships and feeling part of one's community. The findings highlight the importance of examining the multi-factorial constructs of social connectedness and question research attributing loneliness solely to reduced social involvement. As such, interventions for caregivers of a person with dementia need to target feelings of loneliness as well as their social isolation.

Effects of early midlife ovarian removal on sleep: Polysomnography-measured cortical arousal, homeostatic drive, and spindle characteristics

Bilateral salpingo-oophorectomy (BSO; removal of ovaries and fallopian tubes) prior to age 48 is associated with elevated risk for both Alzheimer's disease (AD) and sleep disorders such as insomnia and sleep apnea. In early midlife, individuals with BSO show reduced hippocampal volume, function, and hippocampal-dependent verbal episodic memory performance associated with changes in sleep. It is unknown whether BSO affects fine-grained sleep measurements (sleep microarchitecture) and how these changes might relate to hippocampal-dependent memory. We recruited thirty-six early midlife participants with BSO. Seventeen of these participants were taking 17β-estradiol therapy (BSO+ET) and 19 had never taken ET (BSO). Twenty age-matched control participants with intact ovaries (AMC) were also included. Overnight at-home polysomnography recordings were collected, along with subjective sleep quality and hot flash frequency. Multivariate Partial Least Squares (PLS) analysis was used to assess how sleep varied between groups. Compared to AMC, BSO without ET was associated with significantly decreased time spent in non-rapid eye movement (NREM) stage 2 sleep as well as increased NREM stage 2 and 3 beta power, NREM stage 2 delta power, and spindle power and maximum amplitude. Increased spindle maximum amplitude was negatively correlated with verbal episodic memory performance. Decreased sleep latency, increased sleep efficiency, and increased time spent in rapid eye movement sleep were observed for BSO+ET. Findings suggest there is an association between ovarian hormone loss and sleep microarchitecture, which may contribute to poorer cognitive outcomes and be ameliorated by ET.

Overcoming Barriers to Latino Participation in Alzheimer's Disease Research.

There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

Different meanings of a three-point decline in MMSE score in Alzheimer's disease and depressive disorder.

The Mini-Mental State Examination (MMSE) is a composite scale that is included in diagnostic algorithms and in procedures to assess severity of cognitive impairment and efficacy of therapeutic interventions. It is unclear, however, whether the MMSE provides information about the same deficits in different diseases. To assess patterns of MMSE scores in patients with confirmed diagnosis of Alzheimer's disease or depressive disorder. We used data from a previously published cross-sectional retrospective observational clinical cohort study. The final analysis included only patients in whom biomarker analysis showed results characteristic of Alzheimer's disease (n = 167) and patients with depressive disorder in whom Alzheimer's disease had been ruled out by analysis of biomarkers (n = 69). A three-point decline in MMSE score from 30 to 27 reflected impairment of memory recall in patients with Alzheimer's disease, whereas it reflected impairments in calculation and memory recall in patients with depressive disorder. A further three-point decline in MMSE score from 27 to 24 predominantly reflected additional calculation impairment in patients with Alzheimer's disease. Our results indicate that memory performance is the most important measure of disease severity and the main contributor to the decline in MMSE score at onset of clinical manifestation of Alzheimer's disease. In general, this suggests that memory should be the primary measure used in routine clinical care and the primary endpoint in clinical trials involving patients with Alzheimer's disease at onset of clinical manifestation. Changes in other measures of cognition should prompt consideration of possible comorbidities as a cause, rather than the impact of Alzheimer's disease itself.

Pharmacological Potential of Bioactive Peptides for the Treatment of Diseases Associated with Alzheimer's and Brain Disorders.

Bioactive peptides are a promising class of therapeutics for the treatment of diseases associated with Alzheimer's and brain disorders. These peptides are derived from naturally occurring proteins and have been shown to possess a variety of beneficial properties. They may modulate neurotransmitter systems, reduce inflammation, and improve cognitive performance. In addition, bioactive peptides have the potential to target specific molecular pathways involved in the pathogenesis of Alzheimer's and brain disorders. For example, peptides have been shown to interact with amyloid-beta, a major component of amyloid plaques found in Alzheimer's disease, and have been shown to reduce its accumulation in the brain. Furthermore, peptides have been found to modulate the activity of glutamate receptors, which are important for memory and learning, as well as to inhibit the activity of enzymes involved in the formation of toxic amyloid-beta aggregates. Finally, bioactive peptides have the potential to reduce oxidative stress and inflammation, two major components of many neurological disorders. These peptides could be used alone or in combination with traditional pharmacological treatments to improve the management of diseases associated with Alzheimer's and brain disorders.

The impact of metabolic syndrome on the cerebral cortex: a Mendelian randomization study.

Metabolic syndrome exhibits associations with diverse neurological disorders, and its potential influence on the cerebral cortex may be one of the many potential factors contributing to these adverse outcomes. In this study, we aimed to investigate the causal relationship between metabolic syndrome and changes in cerebral cortex structure using Mendelian randomization analysis. Genome-wide association study data for the 5 components of metabolic syndrome were obtained from individuals of European descent in the UK Biobank. Genome-wide association study data for 34 known cortical functional regions were sourced from the ENIGMA Consortium. Data on Alzheimer's disease, major depression, and anxiety disorder were obtained from the IEU Open genome-wide association study database. The causal links between metabolic syndrome elements and cerebral cortex architecture were evaluated using inverse variance weighting, Mendelian randomization-Egger, and weighted median techniques, with inverse variance weighting as the primary method. Inverse variance weighting, Mendelian randomization Egger, weighted median, simple mode, and weighted mode methods were employed to assess the relationships between metabolic syndrome and neurological diseases (Alzheimer's disease, major depression, and anxiety disorder). Outliers, heterogeneity, and pleiotropy were assessed using Cochran's Q test, MR-PRESSO, leave-one-out analysis, and funnel plots. Globally, no causal link was found between metabolic syndrome and overall cortical thickness or surface area. However, regionally, metabolic syndrome may influence the surface area of specific regions, including the caudal anterior cingulate, postcentral, posterior cingulate, rostral anterior cingulate, isthmus cingulate, superior parietal, rostral middle frontal, middle temporal, insula, pars opercularis, cuneus, and inferior temporal. It may also affect the thickness of the medial orbitofrontal, caudal middle frontal, paracentral, superior frontal, superior parietal, and supramarginal regions. These findings were nominally significant and withstood sensitivity analyses, showing no substantial heterogeneity or pleiotropy. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. This study suggests a potential association between metabolic syndrome and changes in cerebral cortex structure, which may underlie certain neurological disorders. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. Early diagnosis of metabolic syndrome holds significance in preventing these neurological disorders.

Unraveling Amentoflavone's Therapeutic Potential in Alzheimer's Disease: A Preclinical Assessment.

Alzheimer's disease is one of the neurodegenerative diseases which causes cognition deficit. There are currently few medications available to treat Alzheimer's disease, even though researchers have devoted a great deal of time studying the condition and offering many benefits. Thus, only a few drugs are available for the treatment of Alzheimer's disease. Amentoflavone is a dietary component found in many plants and herbs that has several health advantages. Amentoflavone has demonstrated strong protective benefits against a range of brain illnesses in preclinical trials, most frequently in Alzheimer's disease. Amentoflavone, a biflavonoid, can be identified in a variety of herbs upon isolation. Considering the beneficial properties of this compound, this review emphasizes the pharmacological effects and botanical sources of amentoflavone, as well as the compound's benefits and possible applications in the treatment of Alzheimer's disorders.

Daphnetin protects neurons in an Alzheimer disease mouse model and normal rat neurons by inhibiting BACE1 activity and activating the Nrf2/HO-1 pathway.

The common neurodegenerative disorder Alzheimer disease (AD) is characterized by memory dysfunction and cognitive decline in the elderly. Neuropathological features include aggregated β-amyloid (Aβ) accumulation, neuroinflammation, and oxidative stress in the brain. Daphnetin (DAPH), a natural coumarin derivative, has the potential for inhibiting inflammatory and oxidative responses. We explored neuroprotective roles of DAPH treatment in the APP/PS1 transgenic mouse AD model. DAPH ameliorated spatial learning disabilities in Morris water maze tests and reduced Aβ deposition, assessed by immunohistochemistry. It also reduced the Aβ content in supernatants of neurons from fetal APP/PS1 mice, assessed by cell-based soluble ELISA. Molecular docking and fluorescence resonance energy transfer-based assay results suggested that DAPH could directly inhibit BACE1 activity. Furthermore, in vitro experiments utilizing isolated rat neurons assessing RNA expression profiling, immunofluorescence, TUNEL assay, and Western-blot analysis, suggested the potential of DAPH for regulating BDNF and GM-CSF expression and mitigating Aβ1-42-induced cortical injury, synaptic loss, and apoptosis. HO-1 and Nrf2 mRNA and protein expression were also increased in a dose-dependent manner. These results underscore the potential of DAPH as a neuroprotective agent in reversing memory deficits associated with AD and bolster its candidacy as a multitarget natural small-molecule drug for AD patients.

The association between cytomegalovirus infection and neurodegenerative diseases: a prospective cohort using UK Biobank data

Certain viral infections have been linked to the development of neurodegenerative diseases. This study aimed to investigate the association between cytomegalovirus (CMV) infection and five neurodegenerative diseases, spinal muscular atrophy (SMA) and related syndromes, Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and disorders of the autonomic nervous system (DANS). This prospective cohort included white British individuals who underwent CMV testing in the UK Biobank from January 1, 2006 to December 31, 2021. A Cox proportional hazard model was utilized to estimate the future risk of developing five neurodegenerative diseases in individuals with or without CMV infection, adjusted for batch effect, age, sex, and Townsend deprivation index in Model 1, and additionally for type 2 diabetes, cancer, osteoporosis, vitamin D, monocyte count and leukocyte count in Model 2. Bidirectional Mendelian randomization was employed to validate the potential causal relationship between CMV infection and PD. A total of 8346 individuals, consisting of 4620 females (55.4%) and 3726 males (44.6%) who were white British at an average age of 56.74 (8.11), were included in this study. The results showed that CMV infection did not affect the risk of developing AD (model 1: HR [95% CI]=1.01 [0.57, 1.81], P=0.965; model 2: HR=1.00 [0.56, 1.79], P=0.999), SMA and related syndromes (model 1: HR=3.57 [0.64, 19.80], P=0.146; model 2: HR=3.52 [0.63, 19.61], P=0.152), MS (model 1: HR=1.16 [0.45, 2.97], P=0.756; model 2: HR=1.16 [0.45, 2.97], P=0.761) and DANS (model 1: HR=0.65 [0.16, 2.66], P=0.552; model 2: HR=0.65 [0.16, 2.64], P=0.543). Interestingly, it was found that participants who were CMV seronegative had a higher risk of developing PD compared to those who were seropositive (model 1: HR=2.37 [1.25, 4.51], P=0.009; model 2: HR=2.39 [1.25, 4.54], P=0.008) after excluding deceased individuals. This association was notably stronger in males (model 1: HR=3.16 [1.42, 7.07], P=0.005; model 2: HR=3.41 [1.50, 7.71], P=0.003), but no significant difference was observed in the female subgroup (model 1: HR=1.28 [0.40, 4.07], P=0.679; model 2: HR=1.27 [0.40, 4.06], P=0.684). However, a bidirectional Mendelian randomization analysis did not find a genetic association between CMV infection and PD. The study found that males who did not have a CMV infection were at a higher risk of developing PD. The findings provided a new viewpoint on the risk factors for PD and may potentially influence public health approaches for the disease. National Natural Science Foundation of China (81873776), Natural Science Foundation of Guangdong Province, China (2021A1515011681, 2023A1515010495).

Exploring New Schiff Bases: Synthesis, Characterization, and Multifaceted Analysis for Biomedical Applications.

The current work aims to generate novel Schiff bases by reacting substituted aldehydes with amine derivatives catalyzed by a natural acid. The developed compounds underwent diverse physicochemical analyses including liquid chromatography-mass spectrometry, Fourier transform infrared spectroscopy, scanning electron microscopy, 1H- and 13C-nuclear magnetic resonance, and X-ray diffraction. Furthermore, differential thermogravimetric, thermogravimetric, and differential thermal analysis techniques were employed in a nitrogen-free environment to determine kinetic parameters. These data were then used in model-free isoconversional methods (e.g., Friedman, Kissinger-Akahira-Sunose, and Flynn-Wall-Ozawa). The Schiff bases were evaluated for their in vitro and in silico α-amylase inhibitory activity. Schiff base-2 displayed the highest inhibition compared with the reference drug acarbose. In comprehensive MTT assay cytotoxicity investigations, both Schiff bases showed strong anticancer capabilities against the human lung cancer cell line (A549). Moreover, this study demonstrated effectiveness of synthetic compounds in screening Caenorhabditis elegans for anti-Alzheimer's and stress resistance properties. The simplicity of its biology allowed precise evaluation of the effect of compounds on neuronal function and stress response. This research enhances drug discovery efforts for Alzheimer's and stress-related disorders, potentially improving patient outcomes.

Is the Risk of Alzheimer's Disease and Related Dementias Among U.S. Veterans Influenced by the Intersectionality of Housing Status, HIV/AIDS, Hepatitis C, and Psychiatric Disorders?

Homelessness and housing instability disproportionately affect U.S. veterans with psychiatric disorders, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), hepatitis C, and Alzheimer's disease and related disorders (ADRD). We examined housing status and/or HIV/AIDS in relation to ADRD risk and evaluated hepatitis C, substance use, and mental health disorders as mediators and/or moderators of hypothesized relationships, among U.S. veterans ≥50 years of age seeking Department of Veterans Affairs (VA) healthcare services. A retrospective cohort study was conducted using linked VA Homeless Operations Management and Evaluation System and Corporate Data Warehouse databases (2017-2023) on 3 275 098 eligible veterans yielding 133 388 ADRD cases over 5 years of follow-up. Multivariable regression and causal mediation analyses were performed, controlling for demographic and clinical characteristics. Taking stably housed veterans without HIV/AIDS as referent, ADRD risk was higher among veterans with homelessness/housing instability alone (adjusted hazard ratio [aHR] = 1.67, 95% confidence interval [CI]: 1.63,1.72), lower among veterans with HIV/AIDS alone (aHR = 0.65, 95% CI: 0.58,0.73), but similar to veterans with homelessness/housing instability and HIV/AIDS (aHR = 1.01, 95% CI: 0.79,1.29). In adjusted models, hepatitis C and psychiatric disorders were positively related to homelessness/housing instability and ADRD risk, but negatively related to HIV/AIDS. Statistically significant mediation and/or moderation of hepatitis C and psychiatric disorders were observed, although <10% of total effects were explained by these characteristics, controlling for confounders. Among older veterans, ADRD diagnoses over 5 years were less among those with HIV/AIDS, but more among those with homelessness/housing instability, and these relationships were partly explained by hepatitis C and psychiatric disorders.

SCG5 and MITF may be novel markers of copper metabolism immunorelevance in Alzheimer’s disease

The slow-developing neurological disorder Alzheimer’s disease (AD) has no recognized etiology. A bioinformatics investigation verified copper metabolism indicators for AD development. GEO contributed AD-related datasets GSE1297 and GSE5281. Differential expression analysis and WGCNA confirmed biomarker candidate genes. Each immune cell type in AD and control samples was scored using single sample gene set enrichment analysis. Receiver Operating Characteristic (ROC) analysis, short Time-series Expression Miner (STEM) grouping, and expression analysis between control and AD samples discovered copper metabolism indicators that impacted AD progression. We test clinical samples and cellular function to ensure study correctness. Biomarker-targeting miRNAs and lncRNAs were predicted by starBase. Trust website anticipated biomarker-targeting transcription factors. In the end, Cytoscape constructed the TF/miRNA-mRNA and lncRNA-miRNA networks. The DGIdb database predicted biomarker-targeted drugs. We identified 57 differentially expressed copper metabolism-related genes (DE-CMRGs). Next, fourteen copper metabolism indicators impacting AD progression were identified: CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38. A TF/miRNA-mRNA regulation network was then established with two miRNAs (hsa-miR-34a-5p and 34c-5p), six TFs (NFKB1, RELA, MYC, HIF1A, JUN, and SP1), and four biomarkers. The DGIdb database contained 171 drugs targeting ten copper metabolism-relevant biomarkers (BRCA1, MITF, NFKBIA, CD38, CCK2, HPRT1, SPHK1, LDHA, SCG5, and SYT1). Copper metabolism biomarkers CCK, ATP6V1E1, SYT1, LDHA, PAM, HPRT1, SCG5, ATP6V1D, GOT1, NFKBIA, SPHK1, MITF, BRCA1, and CD38 alter AD progression, laying the groundwork for disease pathophysiology and novel AD diagnostic and treatment.

Therapeutical Potential of 5-HT6 of Receptor Modulation in Neurological and Psychiatric Conditions

This review examines the pharmacological effects of targeting 5-HT6 receptors, a subtype of serotonin receptors found primarily in the hippocampus. These receptors are essential for synaptic function, functional plasticity and various cognitive functions such as learning and memory. The review synthesizes the existing literature to investigate the potential therapeutic use of drugs targeting 5-HT6 receptors in neurological and psychiatric conditions, including Alzheimer's disease, schizophrenia, depression, anxiety, neurodegenerative diseases and pregnancy mood disorders. Although some preclinical studies suggest positive precognitive effects, these results have often conflicted with clinical research; therefore more work needs to be done on drug classification and therapeutic effect as well as dosage considerations.

Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer's disease through a systems biology approach and drug repurposing.

The association between Alzheimer's disease and metabolic disorders as significant risk factors is widely acknowledged. However, the intricate molecular mechanism intertwining these conditions remains elusive. To address this knowledge gap, we conducted a thorough investigation using a bioinformatics method to illuminate the molecular connections and pathways that provide novel perspectives on these disorders' pathological and clinical features. Microarray datasets (GSE5281, GSE122063) from the Gene Expression Omnibus (GEO) database facilitated the way to identify genes with differential expression in Alzheimer's disease (141 genes). Leveraging CoreMine, CTD, and Gene Card databases, we extracted genes associated with metabolic conditions, including hypertension, non-alcoholic fatty liver disease, and diabetes. Subsequent analysis uncovered overlapping genes implicated in metabolic conditions and Alzheimer's disease, revealing shared molecular links. We utilized String and HIPPIE databases to visualize these shared genes' protein-protein interactions (PPI) and constructed a PPI network using Cytoscape and MCODE plugin. SPP1, CD44, IGF1, and FLT1 were identified as crucial molecules in the main cluster of Alzheimer's disease and metabolic syndrome. Enrichment analysis by the DAVID dataset was employed and highlighted the SPP1 as a novel target, with its receptor CD44 playing a significant role in the inflammatory cascade and disruption of insulin signaling, contributing to the neurodegenerative aspects of Alzheimer's disease. ECM-receptor interactions, focal adhesion, and the PI3K/Akt pathways may all mediate these effects. Additionally, we investigated potential medications by repurposing the molecular links using the DGIdb database, revealing Tacrolimus and Calcitonin as promising candidates, particularly since they possess binding sites on the SPP1 molecule. In conclusion, our study unveils crucial molecular bridges between metabolic syndrome and AD, providing insights into their pathophysiology for therapeutic interventions.