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PubMed2026

Cross-tissue multi-omics integration highlights BPHL and mitochondrial targets in Alzheimer's disease.

BACKGROUND: Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), yet specific molecular targets remain to be fully characterized. METHODS: A summary-data-based Mendelian randomization (SMR) framework integrated AD genome-wide association study (GWAS) statistics (39,918 cases) with blood DNA methylation quantitative trait loci (mQTL), gene expression (eQTL), and protein (pQTL) data for 1136 mitochondria-related genes. Associations were assessed using Bayesian colocalization and HEIDI testing. Tissue relevance was evaluated in four brain regions (hippocampus, amygdala, cortex, frontal cortex) using GTEx and external transcriptomic datasets. RESULTS: Screening identified eight candidates supported across blood mQTL and eQTL layers. Stepwise central nervous system (CNS) evaluation singled out biphenyl hydrolase-like (BPHL) as the consistent candidate. Higher genetically predicted BPHL expression was associated with reduced AD risk across the hippocampus (OR=0.920, 95% CI 0.873-0.970), amygdala (OR=0.925, 95%CI 0.880-0.973), cortex (OR=0.943, 95% CI 0.908-0.978), and frontal cortex (OR=0.938, 95%CI 0.901-0.976). These findings aligned with protein-protein interactions connecting BPHL to respiratory complexes and lower BPHL expression in independent AD brains. Functional enrichment converged on oxidative phosphorylation pathways. CONCLUSIONS: By integrating multi-omics data with tissue-specific validation, this study nominates BPHL as a consistent protective candidate in the brain. These findings provide genetic support for mitochondrial molecular perturbations in AD, offering insights for future validation.

Alzheimer Disease↗

PubMed2026

Non-coding RNAs and Mitochondrial Dysfunction in Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is responsible for 70% of dementia cases worldwide, with tau hyperphosphorylation and amyloid-β plaque accumulation representing its core pathological hallmarks. Genetic predisposition, oxidative stress, and neuroinflammation contribute to disease onset and progression. Non-coding ribonucleic acids (ncRNAs) are a class of RNAs which control gene expression and whose dysregulation in AD patients has been linked to amyloid production, neuroinflammation, and mitochondrial dysfunction, which ranges from impaired energy metabolism to disrupted mitochondrial biogenesis and dynamics. Our descriptive systematic review surveyed the involvement of ncRNAs in mitochondrial dysfunction in AD across experimental and clinical literature. We identified multiple microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) that directly regulate mitophagy, mitochondrial biogenesis, mitochondrial autophagic, and apoptotic pathways, mitochondrial dynamics, and protein import mechanisms in AD models. Among the most important candidates demonstrating clinical dysregulation, miR-140 and lncRNA NEAT1 regulate mitophagy, while miR-9, miR-34a, miR-146a, miR-155, and miR-485 are implicated in mitochondrial biogenesis and miR-204 in mitochondrial autophagy. LncRNA BDNF-AS, miR-148a-3p, miR-21-5p, and miR-103a-3p emerged as regulators of the mitochondrial apoptosis pathway with confirmed clinical dysregulation. Multiple ncRNAs control mitochondrial dynamics, of which miR-195, miR-124, and miR-455-3p have also been studied in AD patients. Additionally, several ncRNAs were found to indirectly regulate mitochondrial fission, autophagy, and apoptosis, although the underlying mechanisms require further characterization. Thus, while ncRNA-centered AD research is in its early stages, current mechanistic and translational evidence supports mitochondrially relevant ncRNAs as promising candidates for biomarker and therapeutic development.

Alzheimer Disease↗

PubMed2026

Subtle cortical thinning in the temporal pole in middle-aged APOE-ε4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45 ± 3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+ P+ (APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans↗

PubMed2026

Depression and amyloid-β across CSF, PET, and plasma biomarkers: a systematic review and meta-analysis.

Alzheimer's disease is increasingly defined by biomarker evidence of amyloid-β and tau pathology, sharpening questions about whether late-life depression contributes to, or instead reflects, this pathology. We conducted a systematic review and meta-analysis of studies published between 2000 and 2025 that compared amyloid-β biomarkers in adults with and without depression, with depression defined by validated clinical diagnoses or symptom rating scales. Twenty-four studies were included, spanning three biomarker sources: cerebrospinal fluid, positron emission tomography imaging, and plasma. Across all sources, the pooled difference in amyloid-β burden between depressed and non-depressed individuals was small and clustered near zero, indicating only a weak, statistically non-significant tendency toward higher amyloid in depression. When the three sources were examined separately, each yielded a similar near-null result, although between-study heterogeneity was considerable for cerebrospinal fluid and plasma and moderate for imaging. Importantly, a prespecified subgroup analysis showed that imaging results diverged by quantification method: studies using the simpler standardized uptake value ratio clustered around zero, whereas the smaller group of studies using kinetic distribution volume ratio modelling showed a significant positive association, suggesting that methodological choices critically influence the observed relationship. Taken together, these findings indicate that depression is not consistently accompanied by greater amyloid-β burden across widely used biomarker platforms. The distribution volume ratio signal nonetheless raises the possibility of subtle associations that cruder methods may obscure, and suggests that depression may shape Alzheimer's disease trajectories more by modifying the clinical impact of amyloid than by altering its amount.

Humans↗

PubMed2026

Evaluating a coaching intervention for Dementia Care Practice Recommendations in care communities: a cluster randomized controlled trial.

BACKGROUND AND OBJECTIVES: Within care communities, including nursing home and assisted living settings, person-centered dementia care, outlined by the 2018 Alzheimer's Association Dementia Care Practice Recommendations (DCPR), is foundational to quality care and improving staff outcomes. This study evaluates the effectiveness of a 6-month Care Community Coaching Program in enhancing person-centered dementia care and staff outcomes in alignment with the DCPR. RESEARCH DESIGN AND METHODS: A cluster randomized controlled trial was conducted with 77 care communities and 434 staff members-227 from 38 intervention communities and 207 from 39 control communities. Outcomes included employee satisfaction (areas: job satisfaction, team building and communication, scheduling and staffing, training, and management and leadership), person-centered care practices (areas: workplace practices, individualized care and services, caregiver-resident relationships), and dementia care confidence, measured pre- and post-intervention and at 3-month follow-up. A generalized Estimating Equations model was used to estimate intervention effects. RESULTS: Care communities assigned to the coaching intervention showed statistically significant improvements in employee satisfaction and staff perceptions of workplace practices and individualized care. No statistically significant effects on staff perceptions of caregiver-resident relationships or on dementia care confidence were noted. DISCUSSION AND IMPLICATIONS: Findings provide direction for future research and intervention development, including examining coaching's impact on resident quality outcomes, and incorporating skills training into future models. Collectively, findings provide evidence of the effectiveness of a Care Community Coaching Program in improving staff outcomes and person-centered practices, offering a practical path towards improving the lived experience of residents and staff in care communities.

Humans↗

PubMed2026

Age at menopause and subjective cognitive symptoms predict digital cognitive outcomes at the gynecological Well-Woman visit.

INTRODUCTION: Women are at increased risk for Alzheimer's Disease (AD). Growing evidence suggests that the menopausal transition may represent a vulnerable window for development of AD-related pathology. Yet, women are diagnosed with AD later than men. Conducting routine cognitive screenings and integrating information about both cognitive symptoms and age at menopause may help address sex-based disparities in detection and prevention. This study investigated whether subjective cognitive symptoms, in combination with age at menopause, were associated with performance on a digital cognitive task in postmenopausal women. METHODS: 183 postmenopausal women (mean age = 63.8, range = 45-85) were recruited after their Well-Woman visit. Participants completed the Screener for Cognitive Problems in Everyday Life (SCoPE) to assess subjective cognitive symptoms, followed by a sensitive measure of objective cognition: the Linus Health Digital Clock and Recall (DCR™). Information was also collected on age at menopause. We examined associations of subjective cognitive symptoms and age at menopause with digital cognitive performance, adjusting for age, education and depression. Model fit was evaluated using adjusted R2, AIC, and BIC. RESULTS: 48.1% of women reported one or more cognitive symptoms on the SCoPE. On objective testing, 73.2% scored in the normal range, 20.8% in the borderline range, and 6.0% in the impaired range. SCoPE total score was negatively associated with objective cognitive performance in adjusted models (B = -.12, p = .03). Age at menopause showed a significant quadratic association with cognitive performance (B = -0.006, p<.001). SCoPE total was not associated with DCR subtests, while age at menopause predicted both Delayed Recall and Clock Drawing. CONCLUSION: Subjective cognitive symptoms and age at menopause were associated with lower performance on a sensitive, objective cognitive test. Findings support routine cognitive screening and suggest that subjective cognitive symptoms as well as age at menopause are associated with cognitive function.

Humans↗

PubMed2026

Diagnostic value of blood p-tau subtypes in Alzheimer's disease progression and pathology: systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and the most likely to lead to dementia. With the availability of the latest therapies, the need for Alzheimer's disease diagnosis is now gradually increasing. Whereas blood phosphorylated-tau (p-tau) has demonstrated excellent performance in the prediction and diagnosis of disease progression and Aβ positivity in AD, there are differences between different p-tau subtypes. Therefore, a pooled analysis of different blood p-tau subtypes is of more important clinical value. METHOD: Relevant literature was screened by complete search in four databases, Pubmed, Embase, Cochrane Library and Scopus. Relevant data and AUC and their confidence intervals of the included literature were extracted and analyzed by classification according to p-tau subtypes. Quality assessment was performed using the QUADAS-2 tool. RESULT: Our results reveal that p-tau217 performs better in the diagnostic performance in most stages of AD, which is consistent with the guidelines. However, our results concluded that p-tau217 has poorer diagnostic performance in the stages of cognitive unimpaired or less cognitively impaired, especially in the Aβ positivity diagnosis of SCD and CU. Head-to-head meta-analyses formally confirmed that p-tau217 significantly outperforms p-tau181 across AD dementia, Aβ positivity, tau positivity, and biological staging (all P < 0.05), whereas no significant difference was observed between p-tau231 and p-tau181. CONCLUSION: By integrating single-arm pooled AUC estimates with formal head-to-head statistical comparisons, our study provides evidence-based support for plasma p-tau217 as the subtype with the most robust diagnostic performance across AD pathology and biological staging. Head-to-head analyses formally confirmed that p-tau217 significantly outperforms p-tau181 in Aβ positivity, Tau positivity, and biological staging.

Humans↗

PubMed2026

Opposing kinase signaling may underlie the inverse relationship between cancer and Alzheimer's disease.

Cancer and Alzheimer's disease (AD) are leading causes of mortality and exhibit an inverse relationship, where AD patients have reduced cancer risk and vice versa. However, the molecular basis of this relationship remains poorly understood. We reanalyzed published proteomic and phosphoproteomic datasets to investigate this relationship. Differentially abundant proteins were identified in lung adenocarcinoma and glioblastoma samples relative to controls and compared with proteins altered in AD brains, revealing 37 proteins with opposing abundance patterns. Protein-protein interaction and pathway analyses revealed enrichment in kinase signaling and phosphorylation pathways. Phosphoproteomic analysis identified 52 differentially phosphorylated sites with opposing patterns, while kinase-substrate enrichment analysis identified 44 kinases with opposing inferred activity profiles. Integration of kinase activity and phosphosite data identified 29 kinase-phosphosite pairs, including 4 prioritized pairs with opposing patterns relevant to both diseases. Across seven independent cancer cohorts, 17 of 20 statistically significant phosphosite-cohort comparisons (85%) were concordant with the discovery findings, supporting reproducibility of the prioritized phosphosites. Together, these findings highlight opposing kinase signaling as a prominent feature of the inverse relationship and suggest potential biomarkers and therapeutic targets. This study provides a novel systems-level framework for investigating inverse relationships, supported by an R Shiny application for data exploration (https://advscancer.shinyapps.io/advscancer/). SIGNIFICANCE: This study presents an integrated proteomic and phosphoproteomic framework for investigating the inverse relationship between cancer and Alzheimer's disease (AD). By integrating differential protein abundance, phosphosite phosphorylation, inferred kinase activity, and curated kinase-substrate relationships, we identified opposing signaling patterns and prioritized four kinase-phosphosite pairs. Independent evaluation across seven CPTAC cancer cohorts supported the reproducibility of the prioritized phosphosite patterns. These findings provide insight into molecular processes potentially associated with the inverse relationship between cancer and AD, identify candidate biomarkers and therapeutic targets, and demonstrate the value of systems-level, data-driven approaches for investigating shared and opposing disease processes.

Humans↗

PubMed2026

From prediction to mechanism: Explainable AI uncovers plasma and CSF proteomic signatures of Alzheimer's disease.

Alzheimer's disease (AD) plasma and cerebrospinal fluid (CSF) proteomics can distinguish AD from cognitively normal controls, but the generalizability of machine learning performance and the recurrence of biological signals across datasets require cautious interpretation. We developed an explainable artificial intelligence framework spanning two fluids and four ADNI proteomic datasets, covering 2082 modality specific samples, all analysed internally within ADNI. Phase 1 analysed plasma using a 119 analyte NULISA and targeted UPENN panel (n = 727; 216 CE, 511 controls). Phase 2 extended the analysis to CSF using SOMAscan7k, TMT-MS and targeted SET2, with Elecsys Aβ42, Aβ40, total tau and p-tau181 as anchor biomarkers. Only SOMAscan was subject-independent relative to Phase 1 plasma; TMT-MS and SET2 overlapped with Phase 1 for 96.0% and 97.7% of subjects and therefore are not independent replication cohorts. Under subject-level splits with fold internal preprocessing, we compared Elastic Net, Explainable Boosting Machines and gradient boosted trees with SHAP-based explanations. Among the candidate pipelines, we selected the pipeline with the highest held-out test ROC AUC for each platform; the selected values were 0.927 in plasma and 0.954-0.973 across the three CSF datasets. Because the same held out test performance was used for pipeline selection and headline reporting, these are optimistically selected single-holdout estimates, not unbiased estimates of generalizable or clinical performance. Explanations identified five recurring biological axes within ADNI: cholinergic (ACHE), tau/14-3-3 (YWHAG, YWHAZ, YWHAB, YWHAE), neuro-axonal (NEFL, NEFH), microglial/complement (CHIT1, SMOC1, CHI3L1, C7, CFH) and synaptic (NPTXR, NPTX2, DLG4, SYT5, VSNL1, ELAVL2). CSF analyses showed synaptic vesicle-cycle enrichment (q = 2 × 10-6), and CSF YWHAG correlated strongly with total tau (ρ = 0.87). Cross-fluid directional concordance was modest overall (54-57%) but increased to 73-80% among mapped analyte/protein rows reaching q < 0.05 in CSF. These findings provide hypothesis-generating, internally supported evidence within ADNI. Independent external cohorts with locked pipelines are required to evaluate generalizable performance and biological reproducibility; the overlapping TMT-MS and SET2 analyses should not be interpreted as independent replication.

Alzheimer Disease↗

PubMed2026

Psychological impacts of APOE genotype disclosure among Latinos in New York City: a randomized controlled trial.

INTRODUCTION: Latinos face increased Alzheimer's disease (AD) risk but are underrepresented in studies of APOE genotype disclosure. We evaluated the psychological impacts of APOE disclosure in the Información de la Enfermedad de Alzheimer para Latinos (IDEAL) study, a randomized controlled trial among Latinos in New York City. METHODS: Latino northern Manhattan residents without self-reported AD (mean age 52, 69% women, 49% college graduates) were randomized in the period August 2021 to July 2024 to receive AD risk estimates to age 85 incorporating APOE genotype, family history, and ethnicity (disclosure) or the same factors excluding APOE (non-disclosure). Bilingual genetic counselors delivered risk estimates to both groups, unmasked to randomization. Follow-up surveys were completed 6 weeks, 9 months, and 15 months after risk delivery. Primary outcomes were impact of genetic testing in AD (IGT-AD) and Impact of Event Scale-Revised (IES-R). Secondary outcomes were changes from baseline in depression, anxiety, and perceived AD threat. Analyses used intention-to-treat with multiple imputation. RESULTS: Disclosure (N = 194) and non-disclosure (N = 180) groups did not differ on IGT-AD (mean disclosure-non-disclosure difference [MD] at 6 weeks: -1.5, p = 0.14; 9 months: -1.2, p = 0.35; 15 months: -2.0, p = 0.07), IES-R (MD at 6 weeks: 0.00, p = 0.98; 9 months: 0.01, p = 0.84; 15 months: 0.03, p = 0.64), or change in secondary outcomes. Occurrence of disclosure-related adverse events was similar in the disclosure (N = 2) and non-disclosure (N = 3) groups. DISCUSSION: In this Latino cohort, APOE disclosure did not have clinically significant adverse psychological effects, addressing an important evidence gap. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471779.

Aged↗

PubMed2026

Colorimetric gold nanosensors for monitoring protein aggregation: implications for Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It remains a major public health challenge due to the lack of early diagnostic tools and effective disease-modifying therapies. Molecularly, AD is characterized by extracellular amyloid-β (Aβ) plaques and intracellular Tau tangles, as well as soluble oligomers that are likely the neurotoxic species. However, the transient and heterogeneous nature of these oligomers makes them difficult to detect using conventional biosensing approaches. Nanomaterial-based colorimetric biosensors have emerged as promising platforms for detecting protein aggregates and discovering aggregation inhibitors. Specifically, the localized surface plasmon resonance properties of metallic nanomaterials can enable rapid, label-free, and visually detectable colorimetric sensing of molecular interactions. These features can be leveraged to monitor protein aggregation processes in real time and achieve high-throughput screening of aggregation inhibitors, which may collectively enable early detection and timely intervention of AD progression. This Review Article presents the design and engineering of gold-nanomaterial-based colorimetric biosensors for monitoring protein aggregation and highlights the current challenges and emerging opportunities for applying these nanosensors to combat AD.

Journal Article↗

PubMed2026

Assessment of Genetic Correlations Between Tobacco or Alcohol Use and Neurodegenerative Diseases Using East Asian Genetic Ancestry Genome-Wide Association Study Results.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.

Female↗

PubMed2026

Efficacy and safety of Janus kinase inhibitors in Behçet's disease: A systematic literature review.

INTRODUCTION: Behçet's disease e (BD) is a chronic, relapsing, multisystem inflammatory disorder that if not successfully treated can lead to severe, organ or life-threatening complications. Despite treatment with glucocorticoids, immunosuppressants, and tumor necrosis factor (TNF) inhibitors, some patients still have refractory disease that mandates additional therapeutic options. The pathogenesis of BD involves dysregulated innate and adaptive immune responses with multiple cytokines signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. By targeting multiple inflammatory pathways, JAK inhibitors have emerged as a promising therapeutic option. However, current evidence remains limited and heterogeneous. Therefore, we conducted this systematic review to evaluate their efficacy and safety in BD. METHODS: We conducted a systematic literature review in accordance with PRISMA 2020 guidelines (PROSPERO registration: CRD420261381955). PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to March 2026. Original clinical studies evaluating Janus kinase (JAK) inhibitors in BD were included. Two reviewers independently performed study selection, data extraction, and quality assessment using Joanna Briggs Institute tools. Due to heterogeneity, results were synthesized narratively, focusing on efficacy and safety outcomes. RESULTS: Seventeen studies (99 patients) were included, predominantly case reports and small observational cohorts with overall high methodological quality. All evaluated tofacitinib, baricitinib, or upadacitinib, with no data on other JAK inhibitors. Patients were highly treatment-refractory, with prior failure of conventional and biologic therapies. Upadacitinib was the most frequently studied agent and demonstrated an overall response rate of 85.2% and complete remission in 59.3% in a multi-center study. Efficacy was observed across multiple domains, with the most consistent responses in intestinal disease, including clinical and endoscopic remission, alongside frequent glucocorticoid-sparing effects. Safety findings were consistent with known JAK inhibitor safety profiles, with mainly mild to moderate infections and manageable laboratory abnormalities, and no clear signal for increased thrombotic events, although follow-up was limited. CONCLUSION: JAK inhibitors demonstrate promising efficacy in BD, particularly in refractory and multisystem disease. The most consistent evidence of efficacy was observed in gastrointestinal involvement, whereas data for other disease domains remain limited. Their safety profile appears consistent with existing data, although further follow up and validation is required. High-quality randomized controlled studies are an imminent need to study the potential role of JAK inhibitors in BD.

Humans↗

PubMed2026

Nurse-Led Home-Based Mobile Health Cardiac Rehabilitation Program for Patients With Chronic Heart Failure: A Randomized Controlled Trial.

This 12-week randomized controlled trial evaluated a nurse-led mHealth intervention for patients with chronic heart failure, conceptually informed by Riegel's middle-range theory of self-care of chronic illness. The program integrated wearable activity tracking with weekly nurse-led behavioral coaching, reflecting the core self-care processes of monitoring, maintenance, and management. Compared with usual care, the intervention significantly improved daily step count, 6-minute walk distance, metabolic equivalents, and left ventricular ejection fraction. Findings highlight the effectiveness of theory-informed, nurse-delivered mHealth strategies in enhancing physical activity and cardiopulmonary function, while underscoring the critical role of advanced practice nurses in home-based chronic disease management.

Aged↗

PubMed2026

GPR3 in neuro-metabolic-immune-reproductive nexus - a potential therapeutic target for Multi-System diseases.

BACKGROUND: GPR3(G-protein-coupled receptor 3), an orphan G-protein-coupled receptor (GPCR) with constitutive Gs activity, is expressed in the brain, liver, ovary, and other tissues, regulating cell proliferation, differentiation, and apoptosis across the nervous, reproductive, immune, and metabolic systems. This review synthesizes evidence on its integrated signaling and physiological functions to address the lack of a comprehensive multisystem pathophysiology overview. METHODS: A systematic literature search was conducted on PubMed and Web of Science, using keywords such as "GPR3", "GPCR", "neurodegeneration", "metabolism", "immune", "reproduction", "agonist", "inhibitor", and "therapeutic target". This search identified GPR3's roles in neurodegenerative diseases, immune inflammation, reproduction, and energy metabolism. The analysis focused on signaling pathways, ligand regulation, and therapeutic potential. RESULTS: The research indicates that GPR3 is involved in neuronal survival, synaptic plasticity, and microglial activity via the cAMP/PKA, PI3K/Akt, and β - arrestin pathways. It promotes amyloid - β formation in Alzheimer's disease (AD), yet provides neuroprotection in Parkinson's disease (PD) models. It may contribute to anxiety/depression - like states, maintain oocyte meiotic arrest in the ovary, and activate thermogenic genes in adipose tissue. GPR3 modulates immune responses. Using oleic acid (OA) and diphenyleneiodonium (DPI) as activators, and AF64394 and cannabidiol (CBD) as antagonists, it shows potential in disease models. CONCLUSION: GPR3 acts as a central molecular hub integrating neural, metabolic, immune, and reproductive signaling, highlighting its potential as a therapeutic target for chronic multisystem disorders. However, its dual roles in certain pathologies and translation challenges necessitate further research.

Humans↗

PubMed2026

Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies.

BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged ≥ 50 years (n = 7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g = 1.60, 95% CI: 0.95-2.25) and 8-OHdG (g = 2.64, 95% CI: 2.13-3.14) were markedly elevated (p < 0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g = 5.24). In PD, 8-OHdG was moderately elevated (g = 0.78, 95% CI: 0.18-1.39; p = 0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g = 0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.

Humans↗

PubMed2026

Meta-analysis and pharmacoeconomic study of rasagiline versus selegiline in the treatment of Parkinson's disease.

OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16 weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference = -0.82, 95% CI [-2.08, 0.44], p = 0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p = 0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.

Humans↗

PubMed2026

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (χ), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA = 5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans↗

Results for “Alzheimer&#x2019;s Disease”

Results for “Alzheimer’s Disease”