Current Alzheimer research最新文献

{"title":"Cultural Adaptation and Psychometric Properties of the Turkish Version of the Dementia Literacy Assessment (DeLA).","authors":"Fikriye Yılmaz, Emre Ozcan, Deniz Gungor Ozcan","doi":"10.2174/0115672050488853260622072108","DOIUrl":"https://doi.org/10.2174/0115672050488853260622072108","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to culturally adapt the Dementia Literacy Assessment (DeLA) scale into Turkish and to evaluate its psychometric properties. The DeLA introduces an innovative approach by employing narrative-based storytelling, rather than conventional didactic methods, to assess dementia literacy and to challenge prevailing societal misconceptions.</p><p><strong>Methods: </strong>The study comprised procedures including linguistic equivalence testing, expert consensus (ICC = 0.88), and readability analysis. The sample consisted of 120 participants (mean age: 60.88 ± 8.72 years). Participants completed a pre-test, read two culturally adapted stories, and subsequently completed a post-test. Psychometric evaluation included KR-20 reliability coefficients and corrected item-total correlations.</p><p><strong>Results: </strong>The mean DeLA score increased significantly from 7.71 ± 1.95 to 8.54 ± 1.99 (p < 0.05), corresponding to an overall improvement of 14%. The greatest increase was observed among male participants (25.01%). Correct response rates to the statement that \"forgetfulness is a normal part of aging\" improved by 47.3%. The scale demonstrated good internal consistency, with KR-20 values of 0.701 (pre-test) and 0.734 (post-test). Education level, family history of dementia, and caregiving experience were significantly associated with higher post-test performance (p < 0.05).</p><p><strong>Discussion: </strong>Narrative-based assessments such as the DeLA may bridge gaps in dementia knowledge more effectively than traditional approaches by directly addressing deeply rooted cultural myths, including the normalization of forgetfulness.</p><p><strong>Conclusion: </strong>The Turkish version of the DeLA is a valid and reliable instrument with high sensitivity for assessing dementia literacy. Its narrative-based format effectively challenges deeply ingrained cultural misconceptions. The scale offers a robust framework for epidemiological research and public health initiatives aimed at reducing stigma and promoting early diagnosis within Turkey's aging population.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400276","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":"Revisiting Alzheimer's Disease Mechanisms: Amyloid Dynamics, and Emerging Insights.","authors":"Boluwatife Lawrence Afolabi, Adeola Aminat Ajibola, Anne Adebukola Adeyanju, Musbau Adewumi Akanji, Oluyomi Stephen Adeyemi","doi":"10.2174/0115672050395410251029173713","DOIUrl":"https://doi.org/10.2174/0115672050395410251029173713","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by synaptic dysfunction, glial cell activation, and deterioration of neurons. Multiple pathways contribute to its pathophysiology, including β-amyloid (Aβ) plaque formation, intracellular neurofibrillary tangles, oxidative neuronal damage, and inflammatory responses. While Aβ deposition is considered an early trigger in the disease cascade, clinical symptom progression correlates more strongly with tau pathology and inflammatory responses. Recent concerns over data integrity in several high-profile AD studies have prompted critical re-evaluations of widely accepted hypotheses, emphasizing the urgent need for scientific transparency, reproducibility, and independent validation. In compiling this review, we prioritized findings supported by converging evidence from multiple experimental approaches and replication across independent cohorts. The hypothesis that an imbalance between Aβ42 synthesis and clearance is a central factor in AD has gained support from recent evidence, despite ongoing debate over the amyloid β-protein hypothesis. Dominant mutations associated with early-onset AD are primarily found in the amyloid precursor protein, which serves as the substrate for Aβ production, or in presenilin, the protease responsible for Aβ formation. The identification of presenilin as the catalytic site for β-secretase has provided crucial insights into AD pathogenesis. This review synthesizes current understanding of AD mechanisms, highlights emerging insights from multi-omics and spatial transcriptomic technologies, and discusses the evolving therapeutic landscape. Despite setbacks, the field continues to advance through methodological innovation and a revived interest in AD research integrity, offering hope for early diagnosis, more targeted treatments, and ultimately, disease-modifying therapies.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400308","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":"The Role of Digital Health Technologies in Early Detection and Management of Alzheimer's Disease.","authors":"Shima Mehrabadi","doi":"10.2174/0115672050415800251226061142","DOIUrl":"https://doi.org/10.2174/0115672050415800251226061142","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and functional impairment, posing significant challenges for early detection and management. In recent years, digital health technologies have emerged as promising tools to enhance the diagnosis, monitoring, and treatment of AD. This review paper explores the multifaceted role of digital health technologies in the early detection and management of Alzheimer's disease. We examine the use of wearable devices that monitor cognitive function and daily activities, as well as mobile health applications designed for cognitive training and symptom tracking. Additionally, we analyze the impact of telehealth services in providing remote care, particularly for underserved populations. The integration of artificial intelligence and machine learning for analyzing behavioral and cognitive data to support early diagnosis and risk assessment is also discussed. Furthermore, we explore the concept of digital biomarkers and their potential to complement traditional diagnostic methods. Ethical considerations surrounding privacy, data security, and informed consent are addressed to ensure responsible implementation of these technologies. Finally, we highlight gaps in current research and propose future directions for integrating digital health technologies into Alzheimer's care, emphasizing the potential for personalized interventions tailored to individual patient needs. This review underscores the transformative potential of digital health to reshape Alzheimer's disease management and improve patient outcomes.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364714","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":"Quantifying Short-Term Functional Changes After Lecanemab Treatment in Early Alzheimer's Disease: An Exploratory 3-Month Follow-Up Case Report Using Eye Movement and Gait Analysis.","authors":"Yao Li, Kaiyue Xie, Siyv Qian, Zixun Wang, Haining Zhang, Lianghao Si","doi":"10.2174/0115672050471024260520113701","DOIUrl":"https://doi.org/10.2174/0115672050471024260520113701","url":null,"abstract":"<p><strong>Introduction: </strong>Lecanemab is a monoclonal antibody targeting amyloid-β (Aβ) and is currently used in clinical practice for the treatment of early Alzheimer's disease (AD). However, noninvasive biomarkers reflecting its early efficacy are still unclear. This exploratory case report aims to investigate the combination of eye movement and gait analysis to quantitatively monitor shortterm functional changes during lecanemab treatment.</p><p><strong>Case presentation: </strong>Two male patients, both diagnosed with mild Alzheimer's disease through amyloid- PET and both with the APOE ε3/ε3 genotype, received intravenous lecanemab (10 mg/kg, every two weeks) for three months. Cognitive assessments (Montreal Cognitive Assessment, Mini- Mental State Examination, Clinical Dementia Rating), eye movement tests (smooth pursuit, overlapping saccades, anti-saccades), and gait analysis under single-task and dual-task conditions were conducted at baseline and follow-up. Patient 1 (79 years old) showed stable cognitive function, significant improvement in multiple eye movement parameters, and partial improvement in gait under single-task conditions. Patient 2 (60 years old) did not follow up on cognitive function tests as scheduled and showed inconsistent changes in eye movement parameters, but improved selected gait measures under dual-task conditions, particularly a shorter turning time. Neither patient experienced Amyloid-Related Imaging Abnormalities or infusion-related adverse events during the infusion process.</p><p><strong>Conclusion: </strong>This exploratory case report suggests that eye movement and gait analysis may be sensitive to short-term functional changes following lecanemab treatment, which were not consistently captured by traditional cognitive scales. These findings are hypothesis-generating and warrant further investigation in larger studies. Multimodal functional assessment may hold promise as a tool for monitoring early treatment effects in Alzheimer's disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364737","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":"Apolipoprotein E Mimetics in Targeted Drug Delivery: Advances and Therapeutic Potential for Neurodegenerative and Cardiovascular Diseases.","authors":"Chauhan Rishika","doi":"10.2174/0115672050464479260610102042","DOIUrl":"https://doi.org/10.2174/0115672050464479260610102042","url":null,"abstract":"<p><p>The need to improve the delivery of therapeutic compounds that require effective intracranial delivery across the Blood-Brain Barrier (BBB) has generated significant interest in apolipoprotein E (ApoE) mimetic peptides. These synthetic equivalents of the lipid-binding receptorsinteracting domains of natural ApoE are frequently reproducible when incorporated into nanocarriers or nano platforms, including reconstituted low-high density lipoproteins, polymeric nanoparticles, and liposomal systems. The progress in formulation science has led to the development of ApoE- functionalized nanoparticles and multifunctional liposomes with improved BBB translocation, cellular internalization, and Amyloid-beta (Aβ) affinity compared to conventional delivery vehicles. This review provides a comprehensive discussion of the process by which ApoE mimetics can be used to deliver therapeutic drugs and evaluates the different nanocarrier designs adapted to deliver drugs into the nervous system. Emphasis is also placed on new multifunctional systems in which ApoE mimetics are conjugated to therapeutic or diagnostic molecules, enabling imaging of the targeted area, delivery to the disease site, and disease-specific activity. Although the right direction has been taken, several issues still need to be addressed before ApoE-based strategies can be implemented in clinical practice. The problems that continue to limit larger use include formulation stability, unintended off-target interactions, pharmacokinetics, and scalability of complex nanocarrier systems. This review identifies key concerns needed to move ApoE-mimetic technologies toward effective, clinically viable therapies for central nervous system diseases, identifies the issues that inhibit progress, and analyzes possible methods for their management.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304620","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":"Association of Polymorphisms in Genes Involved in Serotonergic Signaling with the Risk of Developing Alzheimer's Disease.","authors":"Ladan Saeb, Seyedehleila Abtahi, Raheleh Masoudi, Ali Javadpour","doi":"10.2174/0115672050459074260331053012","DOIUrl":"https://doi.org/10.2174/0115672050459074260331053012","url":null,"abstract":"<p><strong>Introduction/aim: </strong>Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter involved in mood, learning, and memory regulation. Disruptions in serotonin signaling have been linked to neurodegenerative disorders such as Alzheimer's Disease (AD). This case-control study aimed to examine whether specific polymorphisms in serotonergic genes are associated with AD risk in an Iranian population.</p><p><strong>Materials and methods: </strong>This research employed a case-control observational design to investigate potential associations between serotonin-related gene polymorphisms and the risk of Alzheimer's disease. Blood samples were collected from 68 patients diagnosed with AD and 69 healthy controls from southwest Iran. DNA was extracted, and genotyping for the 5-HT6 receptor gene C267T polymorphism, the 5-HT1A receptor promoter C(-1019)G polymorphism, and the 5- HTTLPR polymorphism in the serotonin transporter gene was performed using PCR with specific primers. Statistical analyses assessed associations between genotypes and AD risk.</p><p><strong>Results: </strong>Statistical analysis showed significant associations between allele and genotype frequencies of these polymorphisms and AD. The T allele of the 5-HT6, C267T polymorphism increased the risk of Alzheimer's disease by 2.3 times (OR = 2.382, p= 0.017). In addition, a positive association was observed between individuals carrying the T allele and an increased risk of developing AD (OR = 2.202, p = 0.049). C allele of C(-1019)G was also associated with increased risk of AD (OR =1.72, p = 0.029). Individuals with the CG genotype (OR = 2.402, p= 0.024) or those carrying the C allele (OR = 2.500, p= 0.015) were more in risk of developing AD. Lastly, while no significant statistical association was found between 5-HTTLPR polymorphism and AD, adjustment for literacy suggested the SL genotype as a potential risk factor (OR = 4.163, p= 0.035).</p><p><strong>Discussion: </strong>Our findings indicate that variations in serotonin-related genes may contribute to Alzheimer's Disease (AD) susceptibility, although their effects appear population-dependent. The 5-HT6 T and 5-HT1A C alleles were associated with a higher risk of AD, while the HTTLPR short allele showed significance only after adjusting for literacy, suggesting that education may influence genetic vulnerability.</p><p><strong>Conclusion: </strong>These results reinforce the multifactorial nature of AD, emphasizing the interaction between genetic and environmental factors. Larger, population-based studies are needed to validate these associations and clarify the mechanisms linking serotonergic signaling to AD pathogenesis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280799","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":"Multitask Sparse Canonical Correlation Analysis and Regression with Parameter Decomposition based on Deep Subspace Reconstruction for Alzheimer's Disease.","authors":"Wei Kong, Pengfei Su, Yufang Xu, Shuaiqun Wang, Kai Wei, Fengchun Ke, Gen Wen, Yaling Yu","doi":"10.2174/0115672050449671260513065443","DOIUrl":"https://doi.org/10.2174/0115672050449671260513065443","url":null,"abstract":"<p><strong>Introduction: </strong>Multimodal imaging genomics overcomes the limitations of singlemodality analyses, offering a more comprehensive understanding of brain pathophysiology. Traditional methods like sparse canonical correlation analysis (SCCA) and its improved versions have been widely used to identify key brain regions and single nucleotide polymorphisms (SNPs) associated with neurodegenerative diseases, such as Alzheimer's disease (AD). However, the fusion of complex and heterogeneous multimodal neuroimages, along with the linear formulation of these methods, limits their ability to capture complex, nonlinear relationships in imaging-genetics data.</p><p><strong>Methods: </strong>To address this limitation, a novel framework, DSR-PDMTSCCAR, is introduced for multimodal AD data. This framework combines deep subspace reconstruction for nonlinear mapping and parameter decomposition to extract modality-consistent and modality-specific features across structural MRI (sMRI) and positron emission tomography (PET) data. Additionally, multitask sparse canonical correlation analysis (MTSCCA) is incorporated to capture correlations across multiple tasks, facilitating modeling of heterogeneous multimodal associations.</p><p><strong>Results: </strong>Evaluations on simulated datasets and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort show that DSR-PDMTSCCAR outperforms conventional methods, including SCCA, partial least squares (PLS), and deep canonical correlation analysis (DCCA). The method identifies biomarkers such as hippocampal and amygdalar alterations in sMRI/PET and APOErelated genetic variants, all consistent with AD pathology.</p><p><strong>Discussion: </strong>The maximum canonical correlation coefficient (CCC) achieved was 0.1759, compared to 0.1525 for MTSCCA. The PET-SNP correlation (0.1896) was more than double that of MTSCCA (0.0864).</p><p><strong>Conclusion: </strong>The DSR-PDMTSCCAR framework offers robust performance in multimodal imaging- genetics analysis, providing enhanced insights into AD pathophysiology and advancing precision medicine.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207378","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":"Long-Term Consequences of Perinatal Asphyxia in the Development of Alzheimer's Disease.","authors":"Agata Tarkowska, Wanda Furmaga-Jabłońska, Ryszard Pluta","doi":"10.2174/0115672050432278251204130006","DOIUrl":"https://doi.org/10.2174/0115672050432278251204130006","url":null,"abstract":"<p><p>Despite remarkable progress in medicine, perinatal asphyxia (PA) remains a significant clinical problem, and concerns regarding its long-term complications are increasingly being raised. Emerging evidence indicates that similar pathological pathways are activated following PA and during neurodegeneration in Alzheimer's disease (AD). These similarities involve various mechanisms, including alterations in AD-related proteins and their gene expression. Disturbances in neurotransmitter function can lead to excitotoxicity and cell death via necrosis and delayed apoptosis. Additionally, as observed in AD, dysregulation of autophagic processes has been reported. Pathological changes initiated by hypoxia in the newborn may trigger chronic neuroinflammation that persists long-term. Similarly, neuroinflammation plays a critical role in the pathogenesis of AD. Other common mechanisms include oxidative stress and mitochondrial dysfunction. Estrogens appear to have a protective effect in both PA and AD; however, ovaries exposed to PA may exhibit a reduced ovarian reserve, potentially diminishing neuroprotection later in life. Epigenetic modifications have also been proposed as a link between PA and AD. This review focuses on the changes that occur in the neonatal brain following PA, with particular emphasis on long-term consequences. We highlight common pathogenetic and causal pathways that may connect PA to the development of AD. Furthermore, we summarize key studies from the past 25 years addressing these topics and briefly discuss current research directions in the treatment of experimental and clinical PA.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201927","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":"Immunotherapeutic Advances in Alzheimer's Disease: The Convergence of Vaccinology and Nanoscience.","authors":"Hanish Singh Jayasingh Chellammal, Ashok Kumar Janakiraman, Dhani Ramachandran, Ronald Darwin Chellappan, Mohamed Saleem Thattakudian Sheikuduman, Madhan Kumar Soutallu Janakiram, Hemanth Kumar Boyina, Mohamed Shabi Mohamed Abdul Kader, Senthil Kumar Kannan, Raju Sugavasi","doi":"10.2174/0115672050415433251106050120","DOIUrl":"https://doi.org/10.2174/0115672050415433251106050120","url":null,"abstract":"<p><p>Amyloid-beta plaques and neurofibrillary tangles promote neuronal dysfunction and cognitive loss, the hallmarks of Alzheimer's disease (AD), a serious global health concern. Current medications offer only symptomatic alleviation, emphasizing the critical need for disease-- modifying therapy. This study was performed using MeSH term search by using keywords, like \"Alzheimer's Disease\", \"AD\", \"Vaccines\", \"Nanoformulations\", \"Amyloid-Beta (Aβ) Vaccines\", \"lecanemab\", \"Tau protein Vaccines\", \"AADvac1\", \"Clinical trials\". The development of vaccines and methods based on nanotechnology is the primary focal point of this review, which explores immunotherapeutic approaches. Active and passive immunization are used in the development of AD vaccines to target tau and amyloid-beta pathology. While passive immunization involves the direct delivery of pre-formed antibodies, active immunization aims to stimulate the patient's own immune system to produce antibodies in response to the antigen. The necessity for effective drug delivery across the blood-brain barrier (BBB), safety issues, and inconsistent efficacy are some of the difficulties facing vaccine delivery strategies. Nanotechnology can overcome the drawbacks of traditional treatments by providing novel approaches for gene therapy, RNA-based interventions, and targeted medication administration. Immunization approaches offer multiple benefits, including regulated and targeted antigen release, as well as stabilizing the vaccine antigens. Therapeutic drugs can be delivered across the BBB, and genes linked to AD can be modulated by nanoparticles and liposomes that resemble exosomes. Current developments, including the incorporation of short Aβ epitopes, liposomal formulations, conformational mimotopes, and virus-- like particles (VLPs), have markedly enhanced vaccine tolerability. Effective AD treatments depend on combination medications, individualized approaches, and ongoing research into crossing the BBB and improving the safety and effectiveness of vaccines.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145891","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":"Mitochondrial Dysfunction in Alzheimer's Disease: Beyond Energy Failure Toward a Pathogenic Nexus.","authors":"Srikruthi Kunigal Sridhar, Prakash Goudanavar, Nimbagal Raghavendra Naveen","doi":"10.2174/0115672050433653251208201102","DOIUrl":"https://doi.org/10.2174/0115672050433653251208201102","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial dysfunction has gained recognition as a central and early event in the pathophysiology of Alzheimer's disease (AD), extending beyond classical energy failure to encompass complex and dynamic perturbations in organelle homeostasis. Despite extensive focus on amyloid-beta (Aβ) and tau, accumulating evidence implicates mitochondria as both targets and amplifiers of neurodegenerative cascades. This review provides a comprehensive synthesis of the mechanistic roles and therapeutic implications of mitochondrial dysfunction in AD, highlighting recent advances and emerging paradigms that underscore mitochondria as integrative nodes in disease onset, progression, and biomarker discovery.</p><p><strong>Materials and methods: </strong>We critically evaluate literature from molecular, cellular, and systemslevel studies-including postmortem brain tissue, transgenic models, and patient-derived cellsfocusing on key domains such as bioenergetic collapse, redox imbalance, mitochondrial dynamics and quality control, Aβ and tau interactions, calcium dysregulation, and apoptosis. Novel mitochondrial mechanisms such as mitochondria-associated membranes (MAMs), mitochondrial unfolded protein response (UPRmt), and mitonuclear communication are discussed alongside recent translational efforts.</p><p><strong>Results: </strong>Alzheimer's disease is characterized by widespread mitochondrial abnormalities, including impaired oxidative phosphorylation, increased reactive oxygen species (ROS), disrupted mitochondrial fission/fusion equilibrium, defective mitophagy, and abnormal calcium buffering. Moreover, direct mitochondrial accumulation of Aβ and tau disrupts protein import, respiratory chain integrity, and transport dynamics.</p><p><strong>Discussion: </strong>These dysfunctions synergistically activate caspase-mediated apoptotic pathways, exacerbating synaptic loss and neuronal death. Promising therapeutic avenues involve antioxidants, NAD+ precursors, mitophagy modulators, and MAM-targeted strategies. Concurrently, mitochondrial biomarkers such as circulating mtDNA, cytochrome c, and neuroimaging via 31P-MRS or PET are emerging as tools for early diagnosis and disease monitoring.</p><p><strong>Conclusion: </strong>Mitochondria constitute a mechanistic nexus in AD, bridging upstream pathological triggers with downstream neurodegeneration. Advancing the field will require patient-specific models (e.g., iPSC-derived neurons, brain organoids), a deeper understanding of mitochondrial heterogeneity, and integration of mitochondrial targets into multi-modal therapeutic strategies. Precision mitochondrial medicine holds promise to transform AD management through mechanismbased diagnosis, stratification, and intervention.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145839","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}