Current Alzheimer research最新文献

{"title":"Efficacy and Safety of Donanemab in the Treatment of Alzheimer's Disease: A Systematic Review and Meta-Analysis.","authors":"Guanqun Hu, Meiyun Zhang","doi":"10.2174/0115672050425914260119063736","DOIUrl":"https://doi.org/10.2174/0115672050425914260119063736","url":null,"abstract":"<p><strong>Introduction: </strong>Donanemab is a monoclonal antibody targeting amyloid-β plaques. This study aims to quantify donanemab's consistent cognitive benefits, biomarker efficacy, and safety risks by pooling data from all available RCTs.</p><p><strong>Materials and methods: </strong>Systematic searches were conducted in PubMed, the Cochrane Library, Web of Science, and Embase. Phase II/III randomized controlled trials comparing donanemab with placebo in amyloid-positive early Alzheimer's disease were included. After screening 133 records, two trials met the inclusion criteria.</p><p><strong>Results: </strong>Donanemab significantly reduced cognitive decline (iADRS +2.93; 95% CI: 1.52- 4.33; P < 0.0001) and functional progression (CDR-SB -0.66; 95% CI: -0.90 to -0.42; P < 0.00001), with amplified benefits in low/medium tau burden patients (iADRS +3.80; 95% CI: 2.10- 5.50). Amyloid clearance was dramatically higher with donanemab (risk ratio (RR) = 234.46; 95% CI: 68.17-806.38; P < 0.00001), with 76.4% achieving amyloid-negative status. There were significantly elevated risks of ARIA-E (RR = 12.90; 95% CI: 8.15-20.43; P < 0.00001), ARIA-H (RR = 2.86; 95% CI: 1.61-5.06; P = 0.0003), and treatment discontinuation (RR = 3.26; 95% CI: 2.38- 4.47; P < 0.00001), whereas all-cause mortality was not significantly different (RR = 1.44; 95% CI: 0.69-3.00).</p><p><strong>Discussion: </strong>Donanemab showed statistically significant cognitive benefits, but its clinical meaningfulness warrants careful interpretation. The iADRS improvement of 2.93 points and the CDRSB reduction in all patients of 0.66 points did not approach their minimal clinically important difference (MCID).</p><p><strong>Conclusion: </strong>Donanemab provides statistically significant but modest benefits in early AD, particularly in low-tau subgroups. However, the magnitude of cognitive and functional improvement did not approach the threshold for a MCID in the overall population, which requires stringent safety monitoring for ARIA. Clinical implementation should prioritize PET stratification and APOEguided surveillance.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between Handwriting Decline and Cognitive-Motor Impairment in Dementia.","authors":"Yury Chernov","doi":"10.2174/0115672050459901260112045555","DOIUrl":"https://doi.org/10.2174/0115672050459901260112045555","url":null,"abstract":"<p><strong>Introduction: </strong>Handwriting reflects the integration of cognitive and motor functions, making it a potential indicator of neurodegenerative changes. Handwriting deterioration often mirrors cognitive and motor decline in dementia, particularly Alzheimer's disease (AD). However, objective assessment methods remain limited. This study is based on the AD-HS instrument, which includes 42 handwriting features and three linguistic features. Their assessment is non-trivial. To ensure an objective and reliable evaluation, the features are given exact and unambiguous definitions. The formal, quantitative association of handwriting dimensions with cognitive and motor changes in dementia enriches previously published statistical results.</p><p><strong>Materials and methods: </strong>Handwriting samples from 53 individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD) were analyzed against a reference group across six dimensions: spatial organization, letter formation, writing dynamics, stroke building, and overall appearance. Statistical analysis determined the significance of each dimension and its contribution to the overall AD-index (ADI).</p><p><strong>Results: </strong>The ADI effectively distinguished dementia samples from the reference group. The strongest diagnostic indicators were found in writing dynamics, followed by letter formation and spatial organization. The characteristics of early deterioration reflect cognitive impairment rather than purely motor impairment, which are less prevalent in the early stages.</p><p><strong>Discussion: </strong>Longitudinal data show that handwriting in early dementia deteriorates gradually, with diagnostic value arising from the combined presence of multiple affected features. The earliest changes appear in dynamic aspects, followed by spatial and organizational deficits, reflecting early cognitive disruption while motor programs remain largely intact. These findings support the validity of the AD-HS instrument for capturing handwriting changes associated with emerging dementia.</p><p><strong>Conclusion: </strong>The ADI offers a concise, quantitative measure of handwriting deterioration related to cognitive decline. Future research should focus on collecting longitudinal data and more strictly differentiating between age-related changes and cognitive decline.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau Protein, α-synuclein, and Amyloid Precursor Protein Processing Genes in the Frontal Cortex of an Ischemic Alzheimer's Disease Model.","authors":"Ryszard Pluta, Anna Bogucka-Kocka, Janusz Kocki, Jacek Bogucki, Stanisław J Czuczwar","doi":"10.2174/0115672050403689251103120712","DOIUrl":"https://doi.org/10.2174/0115672050403689251103120712","url":null,"abstract":"<p><strong>Introduction: </strong>Information regarding the changes in tau protein, α-synuclein, and amyloid precursor protein processing genes in the frontal cortex post-ischemia, cannot be found in literature We decided to examine the expression of these genes in rats after 10-min of cerebral ischemia with survival of 2-30 days and 6-24 months.</p><p><strong>Methods: </strong>Gene expression was assessed by RT-PCR. The relative quantity (RQ) of the studied gene was shown using ΔCT, and the last value was shown as RQ = 2-ΔΔCT.</p><p><strong>Results: </strong>Two days, 12-18 months post-ischemia, the amyloid precursor protein gene was significantly overexpressed. However, the α-secretase gene was significantly overexpressed on day 2 and 12 months post-ischemia. At 1 year post-ischemia β-secretase gene was significantly overexpressed. Presenilin 1 and 2 genes at 2 days, 12 months post-ischemia were significantly overexpressed. At 12-18 months post-ischemia tau protein gene was significantly overexpressed, and at other times it was below control. At 2 days and 12-18 months post-ischemia, the α-synuclein gene was significantly overexpressed, and at other times it was below control.</p><p><strong>Discussion: </strong>The data indicate that after cerebral ischemia, there is no activation of genes that could influence amyloid production in the frontal cortex. However, the data indicate significant activation of tau protein and α-synuclein genes.</p><p><strong>Conclusion: </strong>We revealed non-amyloidogenic metabolism of amyloid precursor protein in the frontal cortex post-ischemia. Moreover, the results showed increased expression of tau protein and α- synuclein genes at 12-18 months post-ischemia, suggesting the involvement of these genes in neurodegenerative processes in the frontal cortex.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"e15672050403689"},"PeriodicalIF":1.9,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Smell Disorder Diagnostics: A Comparative Review of Portable Test Kits and Self-Reported Tools.","authors":"Jayasurya Ramesh, Lakshmi Kanakaraj, Mohammad Badrud Duza","doi":"10.2174/0115672050427159251203090611","DOIUrl":"https://doi.org/10.2174/0115672050427159251203090611","url":null,"abstract":"<p><p><p> Olfactory Dysfunction (OD) is a prevalent yet underdiagnosed sensory disorder with profound implications for quality of life and for the early detection of neurodegenerative diseases such as Parkinson's and Alzheimer's. Beyond its sensory role, OD has emerged as an early, noninvasive biomarker of neurodegenerative pathology, often preceding measurable cognitive decline in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Quantitative smell loss correlates with pathological changes in the olfactory bulb and entorhinal cortex, highlighting its diagnostic potential for early screening and longitudinal monitoring. </p><p> Traditional diagnostic tools, though validated, often require specialized personnel, laboratory infrastructure, and extended testing time, limiting accessibility. This review critically examines recent innovations in the detection of olfactory dysfunction, focusing on portable, user-friendly smell test kits and their comparative performance with self-reported tools such as the Mini Olfactory Questionnaire (Self-MOQ) and 4-CAST. We synthesize evidence on diagnostic reliability, usability, and cultural adaptability, evaluating how these methods align with emerging needs in Alzheimer's and dementia research. </p><p> Portable kits such as PT-Smell and SSomix demonstrate high diagnostic precision and cultural adaptability, while self-administered and self-report tools enable scalable deployment in memory clinics and community screening programs. Within Alzheimer's research, these approaches present practical solutions for early identification of sensory biomarkers linked to cognitive decline. </p><p> To optimize diagnostic integration, a two-step framework is proposed: first-line screening with self-administered tools such as Self-MOQ or 4-CAST, followed by confirmatory psychophysical testing with portable kits such as PT-Smell or SSomix. This tiered model supports early AD and MCI detection, enhances accessibility, and promotes digital health integration for widespread olfactory monitoring. </p>.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Diagnosis of Alzheimer's: Machine Learning Analysis Leveraging Structural MRI.","authors":"Suhail Ahmad Dar, Nasheed Imtiaz, Rameez Ahmad Dar","doi":"10.2174/0115672050421991260125153049","DOIUrl":"https://doi.org/10.2174/0115672050421991260125153049","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Alzheimer's disease (AD) is characterized by significant brain atrophy, detectable via structural MRI. There has been less focus on cortical degeneration in subcortical regional deterioration-particularly during the transition from Mild Cognitive Impairment (MCI) to AD-which remains underexplored. This study aims to identify subcortical regions with progressive atrophy using surface-based morphometry (SBM) and evaluate their potential for early AD diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This longitudinal study collected data from MCI patients (6 months) who later progressed to Alzheimer's within 3 years, alongside healthy controls followed across four time points (6 months-3 years). Reported in line with STARD guidelines, the study aimed to evaluate model performance in distinguishing progressive MCI-to-AD from healthy controls to advance early Alzheimer's diagnosis. The study leveraged the ADNI dataset to analyse 68 subcortical regions in MCI-to-AD converters (MCI-AD) and Healthy Controls (HC) over 6 months to 3 years (i.e., at 6 months, 1 year, 2 years, and 3 years). The groups were classified beforehand using the Clinical Dementia Rating and the Mini-Mental Status Examination scores. Accordingly, three surfacebased morphometry (SBM) metrics-cortical thickness (CTh), gyrification index (GI), and sulcal depth (SD)-were evaluated in the progressive MCI group (individuals with MCI who later converted to Alzheimer's disease) as well as in healthy controls, to quantify morphological changes. Finally, the morphological data were utilized to train and test machine learning models for classification and prediction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Cortical regions exhibiting significant atrophy were identified using paired-samples ttests between 6 months and 3 years. In parallel, machine learning (ML) models were trained and tested on the same dataset to differentiate progressive MCI-to-AD cases from healthy controls across multiple time points (6 months, 1 year, 2 years, and 3 years), and subsequently to predict the progression to Alzheimer's disease. Certain evaluation metrics were considered for the classifier performance, i.e., Accuracy, F1-score, and AUC-ROC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Sub-cortical SBM metrics, particularly CTh, are sensitive to early AD-related atrophy, offering potential biomarkers for disease progression. ML models trained on these features enable accurate classification, with performance peaking near diagnosis-highlighting their utility in early intervention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;SBM-derived subcortical atrophy patterns aid early AD detection and, when combined with ML, offer a scalable predictive framework. Among metrics, CTh showed the greatest decline in MCI-AD, followed by SD and GI. Progressive deterioration was observed in specific subcortical regions, accelerating near diagnosis. Classifiers achieved higher accuracy in distinguishing MCI-AD from HC at later time ","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and Microstructural MRI of Neuroinflammation in Alzheimer's Disease.","authors":"Banafsheh Baniasadipour, Fariba Bagheri, Farzane Hendudari, Soheila Koopaee, Seyed Mohammad Amini, Mahdieh Ahmadi Kamalabadi, Asieh Fatemidokht","doi":"10.2174/0115672050420458251115070244","DOIUrl":"https://doi.org/10.2174/0115672050420458251115070244","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is a leading cause of cognitive decline in older adults, often diagnosed late when pathology and symptoms are established, reducing treatment effectiveness. Both AD and mild cognitive impairment (MCI) trigger neuroinflammation, leading to molecular and microstructural changes, including oxidative stress, mitochondrial dysfunction, glial activation, synaptic and neurotransmitter disturbances, myelin degradation, and white matter dysfunction. The blood-brain barrier (BBB) is also compromised.</p><p><strong>Methods: </strong>Advanced magnetic resonance imaging (MRI) techniques, such as magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), magnetization- transfer imaging (MTI), chemical exchange saturation transfer (CEST), contrast-enhanced MRI (CE-MRI), and arterial spin labeling (ASL), offer promise for the early detection of Alzheimer's disease (AD)-related molecular and microstructural changes.</p><p><strong>Results: </strong>Based on recent studies, advanced MRI modalities-including magnetic resonance spectroscopy, diffusion imaging, contrast-enhanced imaging, and chemical shift imaging-can highlight metabolic dysfunction, white matter degradation, microstructural disruption, blood-brain barrier dysfunction, cerebral hypoperfusion, vascular dysfunction, and pH alterations caused by neuroinflammation in Alzheimer's patients.</p><p><strong>Discussion: </strong>The integration of advanced MRI modalities into clinical practice could improve the diagnosis and management of Alzheimer's disease (AD). Magnetic resonance spectroscopy and diffusion imaging can identify metabolic and microstructural changes years before brain atrophy occurs, aiding professionals in the early detection of AD. Additionally, perfusion imaging and magnetization transfer imaging can help distinguish between Alzheimer's disease, frontotemporal dementia (FTD), and vascular dementia. Finally, contrast-enhanced MRI can monitor the integrity of the blood-brain barrier to evaluate responses to drug treatments.</p><p><strong>Conclusion: </strong>Despite challenges, such as longer scan times and limited specificity, advanced MRIbased approaches are at the forefront of identifying reliable biomarkers for early detection of Alzheimer's disease and determining optimal management and treatment strategies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of GSK-3 Inhibition in Alzheimer's Disease Therapy.","authors":"Hala Algazzawi, Jakleen Abujamai, Asim Muhammad Alshanberi, Rukhsana Satar, Shakeel Ahmed Ansari","doi":"10.2174/0115672050400781250904082943","DOIUrl":"10.2174/0115672050400781250904082943","url":null,"abstract":"<p><p>A serine/threonine kinase with a wide variety of substrates, Glycogen Synthase Kinase-3 (GSK-3) is widely expressed. GSK-3 is a key player in cell metabolism and signaling, modulating numerous cellular functions and playing significant roles in both healthy and diseased states. The two histopathological features of Alzheimer's disease, the intracellular neurofibrillary tangles composed of hyperphosphorylated tau, and the extracellular senile plaques composed of beta-amyloid, have been linked to GSK-3. It alters multiple tau protein locations found in neurofibrillary tangles. Additionally, GSK-3 can react to this peptide and regulate the production of beta-amyloid. The overexpression of GSK-3 in several transgenic models has been linked to tau hyperphosphorylation, neuronal death, and a reduction in cognitive function. It has been shown that lithium, a medication commonly used to treat affective disorders, inhibits at therapeutically relevant concentrations and stops tau phosphorylation. In this review, we provide an overview of the most recent research on the potential of GSK-3 inhibitors for treating Alzheimer's disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"151-160"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Non-coding RNAs in Neurodegeneration: Advances in Therapeutic RNA Modalities and Next-Gen Delivery Technologies.","authors":"Akshay Thakur, Kaunava Roy Chowdhury, Ankush Kumar, Vir Vikram Sharma, Rohit Bhatia","doi":"10.2174/0115672050421604251108045622","DOIUrl":"10.2174/0115672050421604251108045622","url":null,"abstract":"<p><p>Non-coding RNA (ncRNA)-based therapies represent an emerging and transformative approach in the treatment of neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)/Motor Neuron Disease (MND). This review explored the potential for targeting microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and exosomal RNAs, reinforced by promising results from clinical trials demonstrating their capacity to modulate disease pathways. The incorporation of cutting-edge computational methodologies, including RNA structure prediction and gene regulatory network analysis, has been at the forefront in enhancing the efficacy of ncRNA-based treatments. Moreover, chemical methods have improved RNA molecules' stability, accuracy, and directed delivery, enhancing their therapeutic effects. Moreover, cutting-edge RNA editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats/CRISPRassociated protein 13 (CRISPR/Cas13) are advancing our ability to directly manipulate ncRNA expression, offering a powerful avenue for addressing the molecular origins of neurodegeneration. Despite these advances, challenges persist, particularly in ensuring the specificity, delivery efficiency, and long-term efficacy of these treatments. Nanotechnology provides innovative solutions to these obstacles, facilitating more efficient and precise RNA delivery, especially to neuronal tissue. In conclusion, ncRNA-based therapies, while still in nascent stages, represent a hopeful frontier in the fight against NDs. With ongoing research and technological advancements, these therapies could not only halt disease progression but also redefine the future of ND treatment, offering new avenues for patients' care and clinical success.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"245-269"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Alzheimer's Disease Risk Among Latina/o/x Older Adults: A CART Analysis.","authors":"Sung Seek Moon, Javier F Boyas, Jinwon Lee","doi":"10.2174/0115672050413808250930051731","DOIUrl":"10.2174/0115672050413808250930051731","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Alzheimer's Disease (AD) presents a significant public health challenge in the U.S., with Latina/o/x elders being disproportionately affected. This study examines the key risk factors associated with AD in this population.</p><p><strong>Methods: </strong>We analyzed data from the National Alzheimer's Coordinating Center (2017), focusing on 9,801 Latina/o/x older adults (32.7% males and 67.3% females). Statistical analyses conducted included Chi-square tests, t-tests, and Classification and Regression Tree (CART) analysis, which was used as the main statistical tool.</p><p><strong>Results: </strong>The CART model, trained on 70% of the sample and tested on the remaining 30% (N = 9,801), identified seven terminal nodes and selected seven key predictors from 16 candidate variables. The model demonstrated modest discriminative ability (AUC = 0.68 for both training and test sets; misclassification error ≈ 36%). Sensitivity was 75%, while specificity was 55% in the test set. The most important predictors included age, education, smoking history, BMI, hypertension, and use of antidepressant or antipsychotic medications. A critical threshold emerged at < 5.5 years of education, which, in interaction with age and smoking, was associated with notably increased AD risk.</p><p><strong>Conclusion: </strong>This study emphasizes the crucial role of sociodemographic factors-particularly gender, age, and education-in determining AD risk among Latina/o/x elders. CART analysis identified key thresholds for age and education levels impacting AD risk. The findings suggest the need for targeted interventions and policies, with a focus on education and lifestyle factors, to mitigate AD risk in this vulnerable population.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"200-208"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Ascorbic Acid on the Transgenic <i>Drosophila</i> Expressing Human Aβ-42 in the Neurons.","authors":"Yasir Hasan Siddique, Gulshan Ara, Falaq Naz, Himanshi Varshney, Kajal Gaur, Iqra Subhan, Javeria Fatima, Smita Jyoti","doi":"10.2174/0115672050403064251130163451","DOIUrl":"10.2174/0115672050403064251130163451","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aβ) peptides, particularly the toxic Aβ42 isoform. Aβ42 aggregation induces excessive reactive oxygen species (ROS) production, resulting in oxidative damage, lipid peroxidation, protein oxidation, and neuronal dysfunction. Oxidative stress plays a pivotal role in AD pathogenesis, making antioxidants promising therapeutic candidates.</p><p><strong>Objective: </strong>The present study aimed to evaluate the neuroprotective efficacy of ascorbic acid (AA), a potent dietary antioxidant, in a transgenic Drosophila melanogaster model of AD expressing human Aβ42 in neuronal tissues.</p><p><strong>Materials and methods: </strong>Transgenic Drosophila melanogaster expressing human Aβ42 under a neuronal driver were used as the AD model, with wild-type flies as controls. Flies were supplemented with optimized, non-toxic doses of AA throughout their lifespan. Oxidative stress and antioxidant defense were assessed using glutathione (GSH) levels, glutathione S-transferase (GST), thiobarbituric acid-reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), protein carbonyl content (PCC), and acetylcholinesterase (AChE) activity. Locomotor performance was evaluated using the negative geotaxis assay.</p><p><strong>Results: </strong>AA supplementation significantly restored redox homeostasis by increasing GSH levels and reducing TBARS and PCC. Antioxidant enzyme activities (GST, SOD, and CAT) were normalized, accompanied by partial restoration of AChE activity. AA-fed AD flies exhibited improved locomotor performance, delayed cognitive decline, and extended lifespan compared to untreated AD flies.</p><p><strong>Discussion: </strong>The findings indicate that AA mitigates Aβ42-induced oxidative stress by enhancing endogenous antioxidant defenses and reducing oxidative damage. The improvement in AChE activity suggests preservation of cholinergic neurotransmission, which is crucial for learning and memory. Behavioral recovery and lifespan extension further demonstrate the systemic neuroprotective effects of AA, supporting its role as a multifunctional modulator of AD-associated pathology.</p><p><strong>Conclusion: </strong>This study highlights the multidimensional neuroprotective potential of ascorbic acid in a transgenic Drosophila AD model. By alleviating oxidative stress, preserving cholinergic function, improving behavior, and promoting longevity, AA emerges as a promising, low-cost antioxidant for further evaluation in higher animal models and clinical settings.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"142-149"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}