Neurodegenerative disease management最新文献_第3页

Estrogen and progesterone receptor signaling as candidate neuroendocrine modulators in Huntington's disease. 雌激素和孕激素受体信号作为亨廷顿病的候选神经内分泌调节剂。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-29 DOI: 10.1080/17582024.2026.2739334

John Carlson

{"title":"Estrogen and progesterone receptor signaling as candidate neuroendocrine modulators in Huntington's disease.","authors":"John Carlson","doi":"10.1080/17582024.2026.2739334","DOIUrl":"https://doi.org/10.1080/17582024.2026.2739334","url":null,"abstract":"Huntington's disease (HD) is a genetically driven neurodegenerative disorder marked by progressive corticostriatal dysfunction, excitotoxicity, mitochondrial impairment, and neuroinflammation. Disease-modifying therapies remain limited, and the receptor-specific relevance of neuroendocrine signaling is poorly defined.This review evaluates estrogen receptor beta (ERβ), G-protein-coupled estrogen receptor 1 (GPER1), and progesterone-derived neurosteroids, particularly allopregnanolone, as candidate modulators of HD vulnerability. A structured search of PubMed, Web of Science, and Scopus covered studies published from January 1, 1990, through October 1, 2025, supplemented by manual reference screening. Evidence from patients and HD models is prioritized; mechanistic findings from other neurodegenerative and excitotoxic models are interpreted cautiously.We examine receptor-specific effects on glutamatergic signaling, mitochondrial bioenergetics, microglial activation, oxidative stress, and transcription, including potential disruption of estrogen-responsive pathways by mutant huntingtin. Sex differences, hypothalamic-pituitary-gonadal axis disturbances, and neurosteroid fluctuations are also considered.Finally, we assess SERMs, ERβ-selective agonists, and progesterone-based strategies as hypothesis-driven adjuncts-not established treatments-while addressing thromboembolic risk, endocrine contraindications, CNS penetration, receptor selectivity, and drug interactions. This synthesis identifies evidence gaps and proposes testable questions for early-phase translational research.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-13"},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081661","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}

引用次数: 0

Blood-based biomarkers in the anti-amyloid era of Alzheimer's disease: clinical utility, implementation challenges, and future directions. 阿尔茨海默病抗淀粉样蛋白时代的血液生物标志物：临床应用、实施挑战和未来方向

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-26 DOI: 10.1080/17582024.2026.2734618

Bo-Lin Ho, Yuan-Han Yang

{"title":"Blood-based biomarkers in the anti-amyloid era of Alzheimer's disease: clinical utility, implementation challenges, and future directions.","authors":"Bo-Lin Ho, Yuan-Han Yang","doi":"10.1080/17582024.2026.2734618","DOIUrl":"https://doi.org/10.1080/17582024.2026.2734618","url":null,"abstract":"Background: Implementation of disease-modifying anti-amyloid therapies for Alzheimer's disease remains constrained by the cost and procedural burden of positron emission tomography and cerebrospinal fluid testing. This review evaluates blood-based biomarkers in therapeutic pathways.Methods: PubMed/MEDLINE and Embase were searched for literature published from January 2018 onward, with earlier landmark studies included when relevant. Evidence was synthesized on plasma biomarkers in treatment eligibility, biological staging, longitudinal monitoring, therapeutic response, and risk stratification for amyloid-related imaging abnormalities.Results: Among assays, plasma p-tau217 consistently demonstrates the highest diagnostic accuracy for detecting cortical amyloid pathology across clinical settings. The plasma p-tau217/Aβ1-42 ratio is the first blood-based assay cleared by the FDA to identify amyloid pathology, supporting clinical triage. Complementary biomarkers, including plasma Aβ42/40, glial fibrillary acidic protein, and neurofilament light chain, reflect amyloid burden, astroglial activation, and neurodegeneration. Clinical adoption remains limited by inter-assay variability, inconsistent diagnostic thresholds, and the lack of surrogate endpoints for treatment monitoring and adverse-event assessment.Conclusions: Blood-based biomarkers are best incorporated into structured, stepwise diagnostic and therapeutic frameworks rather than replacing established reference standards. Progress will require assay harmonization, prospective validation, and interpretable biomarker-guided care pathways to support scalable, safe implementation of disease-modifying therapies in routine dementia care.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-17"},"PeriodicalIF":2.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063190","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}

引用次数: 0

Epidemiological associations between neurodegeneration and cancer - time to refine our research approach. 神经退行性变与癌症之间的流行病学关联——是时候完善我们的研究方法了。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-26 DOI: 10.1080/17582024.2026.2740131

Jussi Sipilä, Eetu Heervä, Ayla Mehdiyeva, Valtteri Kaasinen

{"title":"Epidemiological associations between neurodegeneration and cancer - time to refine our research approach.","authors":"Jussi Sipilä, Eetu Heervä, Ayla Mehdiyeva, Valtteri Kaasinen","doi":"10.1080/17582024.2026.2740131","DOIUrl":"https://doi.org/10.1080/17582024.2026.2740131","url":null,"abstract":"Cancer and neurodegenerative diseases are devastating aging-related disorders. Epidemiological data suggest a general inverse risk association between them, the mechanisms of which might provide new avenues for developing treatments and prevention strategies. In addition to this observation, meta-analyses have provided some conflicting results, apparently related to disease characterization, data validity, survival bias and unhandled exposure to risk factors. Taking these into account it seems that the association might be specific to certain types of cancers and particular types of neurodegenerative diseases. It should also be noted that, in some cases, the association is positive. Future studies investigating epidemiological association between cancer and neurodegeneration need to take into account several methodological aspects to provide data that can inform basic and translational studies on pathomechanisms. Most importantly, diagnoses must be accurate and validated, disease subtypes should be precisely defined and stratified, sources of possible bias must be explicitly addressed, time-varying trends should be analyzed as potential confounders and null association must always be published.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-7"},"PeriodicalIF":2.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149062923","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}

引用次数: 0

Plasma biomarker and machine learning modeling of clinical progression in cognitively normal individuals at risk for Alzheimer's disease. 认知正常个体阿尔茨海默病风险临床进展的血浆生物标志物和机器学习模型。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-20 DOI: 10.1080/17582024.2026.2731194

Fadi Thabtah, Firuz Kamalov, Robbie Spencer, Neda Abdelhamid, Mohammad Nami

{"title":"Plasma biomarker and machine learning modeling of clinical progression in cognitively normal individuals at risk for Alzheimer's disease.","authors":"Fadi Thabtah, Firuz Kamalov, Robbie Spencer, Neda Abdelhamid, Mohammad Nami","doi":"10.1080/17582024.2026.2731194","DOIUrl":"https://doi.org/10.1080/17582024.2026.2731194","url":null,"abstract":"Aims: To evaluate whether plasma biomarkers can distinguish cognitively normal (CN) individuals who remain clinically stable from those who subsequently develop mild cognitive impairment (MCI) or Alzheimer's disease (AD) and to test the predictive performance of classification data‑driven models.Materials and methods: Plasma biomarker follow-up data from initially CN participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analyzed across Elecsys, Lumipulse, Precivity, and SIMOA assays. Feature selection was done using chi-square, information gain ratio, and ReliefF. K-nearest neighbors (kNN), logistic regression, support vector machine (SVM), and Extreme Gradient Boosting (XGBoost) classifiers were tested using cross-validation. Synthetic Minority Over-sampling Technique (SMOTE) was applied to alleviate class imbalance.Results: pTau217, pTau181, Aβ40, NfL, and assay-specific amyloid/tau ratios have relatively high feature importance. Class imbalance significantly reduced sensitivity in unbalanced models. Following data balancing, the best‑performing SVM model with selected Elecsys features achieved an accuracy of 71.6%, while the highest sensitivity of all models was 56%.Conclusions: Baseline plasma biomarker data, combined with follow-up plasma biomarkers visits can help us identify patterns that are associated with subsequent clinical progression from CN to MCI/AD. However, predictive performance was moderate, and external validation in larger and more diverse cohorts is needed before clinical applications.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-14"},"PeriodicalIF":2.8,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012305","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}

引用次数: 0

Weak association of pathogenic ERBB4 variants with amyotrophic lateral sclerosis. 致病性ERBB4变异与肌萎缩侧索硬化症的弱关联。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-19 DOI: 10.1080/17582024.2026.2736021

Pei-Shan Wang, Sheng-Mei Zou, Qiao Wei, Zhi-Ying Wu, Hong-Fu Li

{"title":"Weak association of pathogenic ERBB4 variants with amyotrophic lateral sclerosis.","authors":"Pei-Shan Wang, Sheng-Mei Zou, Qiao Wei, Zhi-Ying Wu, Hong-Fu Li","doi":"10.1080/17582024.2026.2736021","DOIUrl":"https://doi.org/10.1080/17582024.2026.2736021","url":null,"abstract":"Introduction: ERBB4 variants were reported to cause amyotrophic lateral sclerosis (ALS). However, gene burden analyses did not find an enrichment of rare variants in patients, leaving the pathogenic role of ERBB4 in ALS unclear. Therefore, this study aimed to reassess the association of ERBB4 variants with ALS.Methods: Next-generation sequencing was performed in 250 ALS and 714 non-ALS patients. Low-frequency, deleterious non-synonymous ERBB4 variants were filtered, and their allele frequencies were compared between groups.Results: In total, 42 low-frequency and deleterious ERBB4 variants were identified in patients and normal controls, with three variants in all groups. There was no significant difference in allele frequencies between ALS and non-ALS groups. Additionally, four reported pathogenic variants (c.158A > G, c.284G > A, c.965T > A, and c.1624G > A) were observed in patients with neuromuscular disease or leukoencephalopathy, as well as normal controls. Based on the evidence from this study, c.284G > A was reclassified as a likely benign variant, while the others were reclassified as uncertain significance according to the American College of Medical Genetics and Genomics Guidelines.Discussion: These results suggest a modest association between ERBB4 variants and ALS, underscoring the need for clinicians to conduct more careful molecular diagnosis and genetic consultations for ALS patients with ERBB4 variants.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008773","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}

引用次数: 0

Metabolomic-microbiomic integrated analysis reveals the role of intermittent energy restriction in Parkinson's disease. 代谢组学-微生物学综合分析揭示了间歇性能量限制在帕金森病中的作用。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-18 DOI: 10.1080/17582024.2026.2730172

Kun-Shuo Xu, Hong-Juan You, Ru-Yong Yao, Bing-Hui Hou, Xiao-Yuan Li

{"title":"Metabolomic-microbiomic integrated analysis reveals the role of intermittent energy restriction in Parkinson's disease.","authors":"Kun-Shuo Xu, Hong-Juan You, Ru-Yong Yao, Bing-Hui Hou, Xiao-Yuan Li","doi":"10.1080/17582024.2026.2730172","DOIUrl":"https://doi.org/10.1080/17582024.2026.2730172","url":null,"abstract":"Aims: This study aimed to explore the neuroprotective effect of intermittent energy restriction (IER) on Parkinson's disease (PD) mice via multiomics.Methods: All mice were randomly divided into four groups: the control group, the PD model group, the PD+IER group and the PD+L-Dopa group. A multi-omics strategy combining 16S rRNA sequencing and fecal metabolomics, together with molecular biological validation (Western blotting and immunohistochemistry), was employed to systematically investigate the protective effects of IER against PD in mice and the underlying mechanisms.Results: The results showed that IER significantly reshaped the gut microbiota structure of PD mice, with enrichment of Clostridia and Peptostreptococcaceae. Metabolomic analysis further revealed that IER elevated the levels of beneficial intestinal metabolites mainly by regulating the GnRH secretion pathway and the serotonergic synaptic pathway, as well as by modulating signal transduction and amino acid metabolism. Notably, IER simultaneously decreased the expression of Parkin and HIF-1α in both intestinal and brain tissues.Conclusions: The present study demonstrates that IER exerts neuroprotective effects to delay PD progression by regulating the gut microbiota-metabolite axis and targeting key proteins involved in PD pathogenesis. These findings provide experimental evidence and novel mechanistic insights into dietary intervention for PD.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-14"},"PeriodicalIF":2.8,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990823","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}

引用次数: 0

Chronic psychostimulant exposure and vulnerability to Parkinson's disease: is there a role for brain iron? 慢性精神兴奋剂暴露与帕金森病易感性：脑铁是否有作用？

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-16 DOI: 10.1080/17582024.2026.2734624

Hugo A E Morandini, Marcel Schulze, Scott Ayton, Lena Smirnova, Tim J Silk, Pradeep Rao

{"title":"Chronic psychostimulant exposure and vulnerability to Parkinson's disease: is there a role for brain iron?","authors":"Hugo A E Morandini, Marcel Schulze, Scott Ayton, Lena Smirnova, Tim J Silk, Pradeep Rao","doi":"10.1080/17582024.2026.2734624","DOIUrl":"https://doi.org/10.1080/17582024.2026.2734624","url":null,"abstract":"Alterations in brain iron homeostasis have been reported in Parkinson's disease (PD) and Attention Deficit/Hyperactivity Disorder (ADHD). Recent evidence suggests a potential link between ADHD and an increased risk of PD onset, with psychostimulant exposure--particularly methylphenidate (MPH)--as a possible contributing factor. A growing body of evidence indicates an association between chronic MPH exposure and increased striatal and nigral iron content in children with ADHD. Elevated iron levels in the nigrostriatal pathway are thought to contribute to PD pathophysiology. In this perspective paper, we describe the interplay between dopamine autoxidation, inhibition of mitochondrial complex I, and increased cellular iron accumulation. We then discuss how alterations in membrane transporters following chronic MPH exposure may disrupt dopamine compartmentalization and promote dopamine autoxidation in nigrostriatal dopaminergic terminals. Finally, we review preliminary neuroimaging evidence of increased nigrostriatal iron content in predominantly MPH-medicated children with ADHD compared with medication-naïve children and neurotypical controls, and we propose recommendations to further evaluate this putative relationship. Importantly, evidence is preliminary, and the proposed hypothetical model should not be used to guide clinical practice currently.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983389","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}

引用次数: 0

Non-invasive brain stimulation in amyotrophic lateral sclerosis: a systematic review and meta-analysis of transcranial direct current stimulation and transcranial magnetic stimulation. 无创脑刺激治疗肌萎缩侧索硬化症：经颅直流电刺激和经颅磁刺激的系统回顾和荟萃分析。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-09-10 DOI: 10.1080/17582024.2026.2731195

Bassel Alrabadi, Hasan I Matar, Natalie Bandak, Said Yaseen, Aseel Badwan, Omar Alomari

{"title":"Non-invasive brain stimulation in amyotrophic lateral sclerosis: a systematic review and meta-analysis of transcranial direct current stimulation and transcranial magnetic stimulation.","authors":"Bassel Alrabadi, Hasan I Matar, Natalie Bandak, Said Yaseen, Aseel Badwan, Omar Alomari","doi":"10.1080/17582024.2026.2731195","DOIUrl":"https://doi.org/10.1080/17582024.2026.2731195","url":null,"abstract":"Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with limited disease-modifying treatments. Noninvasive brain stimulation techniques have been investigated as potential neuromodulatory interventions targeting cortical hyperexcitability in ALS.Objective: To systematically evaluate the clinical efficacy, neurophysiological effects, and safety of tDCS and TMS-based interventions in ALS.Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Scopus, Web of Science, and Cochrane Library were searched from inception to March 2026.Results: Thirty studies involving ALS patients were included. Pooled analyses showed no significant difference between active stimulation and sham in ALSFRS-R at 6 months (MD = 0.58, 95% CI - 0.16 to 1.31) or at end of follow-up (MD = 0.20, 95% CI - 0.49 to 0.89). No significant effect was observed for manual muscle testing. Considerable heterogeneity was noted across studies. However, several studies demonstrated modulation of cortical excitability and intracortical inhibitory circuits, particularly with repeated stimulation protocols. Both tDCS and TMS were consistently safe and well tolerated, with no serious adverse events reported.Conclusion: Noninvasive brain stimulation in ALS does not significantly improve functional outcomes, but induces measurable neurophysiological changes with a strong safety profile. Further studies should optimize protocols and identify responsive subgroups.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-13"},"PeriodicalIF":2.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930715","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}

引用次数: 0

Clinical correlates of APOE ε4 homozygosity in Alzheimer's dementia: findings from an Indian cohort. APOE ε4纯合性与阿尔茨海默病痴呆的临床相关性：来自印度队列的研究结果

IF 2.8

Neurodegenerative disease management Pub Date : 2026-08-31 DOI: 10.1080/17582024.2026.2723525

Pratibha Vinod, Chidatma Arampady, Somdatta Sen, Meghana Janardhanan, Lakshmi Narayanan Kota, Suhas Ganesh, Pavithra Jayasankar, Bhagyalakshmi Shankarappa, Pradip Paul, Swarna Buddha Nayok, Nikhilan J, Vasundhra Teotia, Tallapally Manideepika, Biju Viswanath, Jayant Mahadevan, Palanimuthu Thangaraju Sivakumar, Srikala Bharath, Mathew Varghese, Sanjeev Jain, Meera Purushottam

{"title":"Clinical correlates of APOE ε4 homozygosity in Alzheimer's dementia: findings from an Indian cohort.","authors":"Pratibha Vinod, Chidatma Arampady, Somdatta Sen, Meghana Janardhanan, Lakshmi Narayanan Kota, Suhas Ganesh, Pavithra Jayasankar, Bhagyalakshmi Shankarappa, Pradip Paul, Swarna Buddha Nayok, Nikhilan J, Vasundhra Teotia, Tallapally Manideepika, Biju Viswanath, Jayant Mahadevan, Palanimuthu Thangaraju Sivakumar, Srikala Bharath, Mathew Varghese, Sanjeev Jain, Meera Purushottam","doi":"10.1080/17582024.2026.2723525","DOIUrl":"https://doi.org/10.1080/17582024.2026.2723525","url":null,"abstract":"Aim: The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD), with a gene-dose effect, but its prevalence and clinical correlates in remain underexplored in South Asians. We examined APOE ε4 homozygosity and its clinical correlates in Indian cohort.Patients and methods: We analyzed APOE genotype data from 393 patients with AD and 850 age-matched healthy controls from India. Variables included family history of dementia, age at onset, behavioral and psychological symptoms of dementia (BPSD), comorbidities (Diabetes and Hypertension), and severity on the Hindi Mental Status Examination (HMSE) and Clinical Dementia Rating (CDR) scale.Results: APOE ε4 allele frequency was higher in patients with AD (25%) than controls (9%); homozygosity was also more frequent among patients (5% vs 1%; X2 = 103.48, p < 0.001). Homozygosity was associated with family history of dementia, [Odds Ratio (OR) 4.03, 95% CI 1.46-11.10, p = 0.007], consistent on Firth analysis, but not with age at onset, duration, severity, BPSD, or comorbidities.Conclusion: In this Indian cohort, APOE ε4 homozygosity reflects increased susceptibility and familial aggregation of AD but does not confer a more severe or distinct phenotype, suggesting ancestry- specific expression of APOE ε4 gene-dose effects.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-6"},"PeriodicalIF":2.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866134","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}

引用次数: 0

High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications. 大剂量甲钴胺治疗肌萎缩性侧索硬化症：机制原理、转化证据和临床意义。

IF 2.8

Neurodegenerative disease management Pub Date : 2026-08-27 DOI: 10.1080/17582024.2026.2713755

Alexandre Almeida da Silva, Camila Castelo Branco Pupe, Júlio César Claudino Dos Santos

{"title":"High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications.","authors":"Alexandre Almeida da Silva, Camila Castelo Branco Pupe, Júlio César Claudino Dos Santos","doi":"10.1080/17582024.2026.2713755","DOIUrl":"https://doi.org/10.1080/17582024.2026.2713755","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder characterized by selective degeneration of upper and lower motor neurons, driven by converging mechanisms including glutamatergic excitotoxicity, mitochondrial dysfunction, oxidative stress, calcium dyshomeostasis, impaired RNA metabolism, and neuroinflammation. In the absence of effective disease-modifying therapies, high-dose methylcobalamin has emerged as a candidate intervention based on its pleiotropic neurobiological effects. A structured literature search was conducted in PubMed/MEDLINE and ScienceDirect to identify peer-reviewed studies published between January 2017 and December 2025 addressing the mechanistic, preclinical, and clinical effects of methylcobalamin in ALS. Preclinical evidence suggests that methylcobalamin modulates homocysteine metabolism, supports S-adenosylmethionine-dependent methylation pathways, preserves mitochondrial integrity, attenuates oxidative stress, and promotes axonal regeneration. Experimental and translational findings further indicate that its therapeutic effects may be strongly dose dependent, particularly under ultra-high-dose regimens capable of overcoming limitations in central nervous system delivery. Clinical trials evaluating ultra-high-dose methylcobalamin demonstrate a potential attenuation of functional decline in patients treated during early disease stages, although effects on survival and respiratory outcomes remain inconsistent. This narrative review integrates molecular mechanisms, experimental evidence, biomarker research, and clinical trial data to examine the translational relevance, stage dependency, and therapeutic implications of high-dose methylcobalamin in ALS.","PeriodicalId":19114,"journal":{"name":"Neurodegenerative disease management","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831165","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}

引用次数: 0