Journal of Alzheimer's disease reports最新文献

{"title":"A novel <i>PSEN2</i> mutation in amnestic early-onset Alzheimer's disease (EOAD): A familial case series.","authors":"Carl Froilan D Leochico, Ekaterina Rogaeva, Ljubica Zotovic, Ana Luiza Pinto Oliveira, Tina Le, Amit Singnurkar, Mario Masellis, Sara B Mitchell","doi":"10.1177/25424823251348676","DOIUrl":"10.1177/25424823251348676","url":null,"abstract":"<p><p>Familial early-onset Alzheimer's disease (EOAD) is a rare form of dementia often caused by autosomal dominant mutations in <i>APP</i>, <i>PSEN1,</i> or <i>PSEN2</i>. We report a novel <i>PSEN2</i> missense variant (c.359T > G, p.Ile120Ser) that has been detected in four siblings; three of whom are affected by predominantly amnestic EOAD or mild cognitive impairment in their fifties (supported by neuroimaging biomarkers), while the youngest sibling is currently asymptomatic at age 50. Two of the siblings were also heterozygous for a variant in <i>PSEN1</i> (c.118_120del, p.Asp40del). Between the two genes, the <i>PSEN2</i> variant was deemed to be likely pathogenic based on segregation with EOAD, imaging biomarker analyses, and bioinformatic analyses. Reporting genetic findings in familial EOAD cases can help in classifying their pathogenic significance and improving genetic conceptualization within Alzheimer's disease.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251348676"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509840","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":"miR-137: A therapeutic candidate or a key molecular regulator in Alzheimer's disease?","authors":"Muhammad Wasim, Junhao Guo, Zhendong Wang, Rabia Parveen, Riling Chen, Yajun Wang, Guoda Ma","doi":"10.1177/25424823251352166","DOIUrl":"10.1177/25424823251352166","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder driven by amyloid-β accumulation, tau pathology, and synaptic dysfunction. Recent studies highlight miR-137, a brain-enriched microRNA, as a pivotal regulator of AD pathogenesis. This review synthesizes evidence that miR-137 modulates amyloid-β production, tau phosphorylation, synaptic plasticity, and neuroinflammation, while also preserving mitochondrial function and mitigating oxidative stress. Notably, circulating miR-137 levels correlate with AD progression, offering promise as a non-invasive diagnostic biomarker. Beyond diagnostics, miR-137's ability to target multiple AD-related pathways positions it as a novel therapeutic candidate for neuroprotection. Hence, miR-137 serves as both a biomarker and therapeutic target, offering promising strategies to slow AD progression and improve outcomes. Our bioinformatic analyses further identify miR-137-regulated genes and disrupted networks, underscoring its central role in AD. By bridging molecular mechanisms and clinical potential, miR-137-based strategies could transform AD management, addressing both pathological hallmarks and cognitive decline. Hence, this review article consolidates evidence of miR-137's multifaceted functions in AD, encouraging further investigation into its molecular mechanisms and translational potential to address this pathogenic condition.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251352166"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509842","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":"Insights into the role of cerebrospinal fluid cytokines in Alzheimer's disease: A commentary on recent findings.","authors":"Carlo Manco, Matteo Pardini, Delia Righi, Domenico Plantone","doi":"10.1177/25424823251352846","DOIUrl":"10.1177/25424823251352846","url":null,"abstract":"<p><p>We read the study by Bruno et al. (2025), which highlights the interplay between neuroinflammation and cortical activity in Alzheimer's disease (AD). Their findings on IL-4, IL-7, IL-8, and IL-12 levels and their association with EEG alterations complement our recent research on IL-6, GDF-15, and neuronal damage. We discuss the implications of IL-8 in blood-brain barrier permeability and neurodegeneration, the role of <i>APOE4</i> in epilepsy-related phenotypes, and the need for better patient stratification. Future studies should explore these inflammatory pathways to clarify the relationship between neurodegeneration and interictal epileptiform discharges in AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251352846"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509841","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":"Predicting brain health in community-dwelling elderly populations by integrating Gaussian mixture model and plasma biomarkers.","authors":"Yue Wang, Tianshu Zhu, Qian Cheng, Xiaolin Cui, Pengfei Zhang, Zhiming Lu","doi":"10.1177/25424823251331110","DOIUrl":"10.1177/25424823251331110","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most common type of dementia, and early screening is crucial for intervention.</p><p><strong>Objective: </strong>Currently, early screening for older adults without dementia primarily rely on cognitive scale. This study aims to explore a more feasible approach.</p><p><strong>Methods: </strong>Plasma biomarkers (Aβ_42/40, p-tau181 and p-tau217) and Gaussian mixture models (GMM) were utilized for stratifying risk levels in older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative. Linear mixed effects model was employed to compare subsequent pathological and cognitive changes, alongside a comparison with traditional scale-based screening methods. Cox regression model was used to assess the risk of progression to dementia across different biomarker status groups.</p><p><strong>Results: </strong>Plasma Aβ_42/40 and p-tau217 effectively predicted Aβ PET pathological progression, while p-tau217 also predicted tau PET changes. All three biomarkers could forecast the progression of FDG PET and cognitive function. P-tau217 and p-tau181 significantly modulated pathology-related cognitive impairment. All three biomarkers could predict dementia risk. The screening method combining GMM with plasma biomarkers demonstrates superior predictive ability compared to traditional scale-based approaches.</p><p><strong>Conclusions: </strong>Our study indicated that the combination of GMM and plasma biomarkers for community screening shows promising potential in monitoring brain health among older adults without dementia. P-tau217 exhibited the best predictive value among the three plasma biomarkers.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251331110"},"PeriodicalIF":2.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499744","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":"γ-secretase targeting in Alzheimer's disease.","authors":"Lin Du, Ge Li, Yinxiang Wei, Gencheng Han","doi":"10.1177/25424823251349529","DOIUrl":"10.1177/25424823251349529","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders and is characterized by memory loss and cognitive decline. The amyloid cascade hypothesis posits that the pathogenesis of AD is initiated by the oligomerization and accumulation of toxic amyloid-β (Aβ) peptides within the brain. The aspartic protease γ-secretase, which catalyzes the final step in the cellular production of Aβ peptides, has been identified as a potential target for anti-amyloid intervention strategies. This target has attracted increasing attention in recent years, and novel small molecules have been developed as selective γ-secretase inhibitors and γ-secretase modulators. This review aims to discuss the role of γ-secretase protein hydrolysis activity in the pathogenesis of AD and to review the molecular mechanisms and prospects for the future development of strategies that target γ-secretase to intervene in AD development, which is expected to provide new ideas for the treatment of AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251349529"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499745","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":"Education and age of decline in verbal memory across countries: Evidence from the HRS, MHAS, and CHARLS.","authors":"Chengming Han, Octavio N Bramajo, Brian Downer","doi":"10.1177/25424823251351631","DOIUrl":"10.1177/25424823251351631","url":null,"abstract":"<p><strong>Background: </strong>Despite the well-established association between education and cognition in old age, age-related changes in cognition by education across different contexts remain underexplored.</p><p><strong>Objective: </strong>This study investigates cross-national differences in decline in verbal memory among adults aged 50 and older in the United States, Mexico, and China.</p><p><strong>Methods: </strong>Data come from the Health and Retirement Study (HRS, 2012-2020), Mexican Health and Aging Study (MHAS, 2012-2021), and China Health and Retirement Longitudinal Study (CHARLS, 2011-2020). Multilevel models estimated changes in verbal memory across six age groups and six educational levels, adjusting for physical health, residence, and gender.</p><p><strong>Results: </strong>HRS participants had the highest educational attainment, while CHARLS participants had the lowest. Higher education was associated with better verbal memory, with the most pronounced education gradient in the CHARLS. Declines in verbal memory were steeper for MHAS and CHARLS participants over 60 compared to HRS participants. MHAS participants experienced earlier declines in verbal memory across all education levels compared to HRS and CHARLS participants.</p><p><strong>Conclusions: </strong>Middle-aged and older adults in Mexico experienced earlier declines in verbal memory after age 50 compared to those in China and the United States. Future research should seek to identify other potentially modifiable factors that may contribute to cross-national differences in decline in verbal memory.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251351631"},"PeriodicalIF":2.8,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478068","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":"Comparison between treatment-placebo difference and saved time measures to assess treatment effect in Alzheimer's disease.","authors":"Guogen Shan, Yahui Zhang, Guoqiao Wang","doi":"10.1177/25424823251349242","DOIUrl":"10.1177/25424823251349242","url":null,"abstract":"<p><strong>Background: </strong>The estimated treatment-placebo difference from fitted statistical models is often used to evaluate the treatment effect. In addition, we may use time saving as an alternative measure to assess the treatment benefit to patients. Two methods were developed to estimate saved time based on the placebo or treatment disease progression curve.</p><p><strong>Objective: </strong>In this article, we are interested in comparing the performance of the traditional model and saved time measures with regards to the statistical hypothesis testing.</p><p><strong>Methods: </strong>By mimicking data from the Phase 2 and 3 donanemab trials, we studied three different treatment disease progression trajectories.</p><p><strong>Results: </strong>The traditional treatment-placebo difference model often has higher statistical power values than the saved time methods when sample size is small to medium. As sample size goes up, saved time methods have similar statistical power and they could be more powerful than the traditional model in some cases.</p><p><strong>Conclusions: </strong>Saved time methods may be considered in future Alzheimer's disease trials to improve the efficiency in drug discovery.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251349242"},"PeriodicalIF":2.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287461","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":"Studies on curcumin-glucoside in the prevention of alpha-synuclein aggregation.","authors":"Lakshmi Sowmya Emani, Jayanth K Rao, Jagadeesha Kumar Dasappa, Marisín Pecchio, Johant Lakey-Beitia, Hansapani Rodriguez, Jessica Cruz-Mora, Priya Narayan, Nikhilesh Anand, Govindaraju Mullur, Rajanna Ajumeera, Bharathi S Gadad, Jagannatha Rao Kosagisharaf","doi":"10.1177/25424823251347260","DOIUrl":"10.1177/25424823251347260","url":null,"abstract":"<p><strong>Background: </strong>α-synuclein (α-syn) deposition in the mid-brain region is one of the hallmark pathologies of Parkinson's disease (PD). The key steps involve the transformation of α-synuclein into a toxic oligomer and insoluble fibrillar aggregates.</p><p><strong>Objective: </strong>To understand the role of curcumin-glucoside in the prevention of α-syn aggregation, a mechanistic approach.</p><p><strong>Methods: </strong>In the present study, we synthesized a novel molecule, curcumin-glucoside (Curc-gluc), to improve the water solubility and partition coefficient, making the molecule with high bioavailability. The present study is focused on understanding the α-syn aggregation kinetics in the presence and absence of Curc-gluc, curcumin (Cur), copper (Cu), and iron (Fe) through Thioflavin T analysis, circular dichroism (CD), mathematical approach by self-association kinetics, and molecular docking models.</p><p><strong>Results: </strong>The results indicated that Curc-gluc potentially prevented synuclein aggregation compared to Curc alone and inhibited Cu and Fe-induced synuclein aggregation. CD studies indicated that Curc-gluc favored α-helix formation. The docking studies indicated that Curc-gluc derivatives interacted with various chains of α-syn fibrils, namely G-chain, A-chain, I-Chain, and E-chain and the Pi-Pi interaction indicate that, Curc-gluc shows the most favorable binding affinity with the α-syn fibrils with 60.7222 kcal/mol of -CDOCKER_ ENERGY and 89.6516 kcal/mol of -CDOCKER INTERACTION_ ENERGY. The Absorption, Distribution, Metabolism, Excretion (ADME) analysis indicated that Curc-mono and di-gluc have the highest solubility, bioavailability, and tissue distribution compared to Curc alone.</p><p><strong>Conclusions: </strong>The studies indicated that Curc-gluc prevented α-syn aggregation by favoring α-helix, binding to α-syn, and preventing aggregation, and had high bioavailability.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251347260"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276933","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":"Exploring the physiotherapy and exercise needs and preferences of nursing home residents with dementia: A qualitative study.","authors":"Dennis Boer, Romée Nibbering, Charlotte Schmidt, Shanty Sterke, Eefje Sizoo, Wilco Achterberg, Thea Vliet Vlieland","doi":"10.1177/25424823251349166","DOIUrl":"10.1177/25424823251349166","url":null,"abstract":"<p><strong>Background: </strong>Exercise is widely employed to prevent functional decline in individuals with Alzheimer's disease and other forms of dementia. Exercise interventions are often supervised by physiotherapists, particularly in Western countries. However, adherence to exercise-based interventions remains suboptimal, particularly among nursing home residents.</p><p><strong>Objective: </strong>To investigate the needs and preferences of nursing home residents with mild to moderate dementia concerning physiotherapy and exercise interventions.</p><p><strong>Methods: </strong>Semi-structured individual interviews were conducted with 12 residents from various nursing homes who had been diagnosed with mild to moderate dementia, were proficient in Dutch, and capable of providing informed consent. Data from the interviews were analyzed using thematic analysis.</p><p><strong>Results: </strong>Four key themes were identified: perceptions of physiotherapy and preferences for physiotherapy sessions, defining physiotherapy and exercise, exercise without physiotherapist supervision, and communication. In general, residents preferred physiotherapy that incorporated exercise and guidance aimed at preserving their independent physical functioning. Physiotherapy was perceived as more intensive than general exercise classes, and not necessarily suitable for all residents. Participants indicated that, provided safety and quality were maintained, they were willing to perform exercises independently. Residents expressed a desire for their family caregivers to be kept informed about their therapy, although they largely preferred to exercise with another person.</p><p><strong>Conclusions: </strong>Nursing home residents with mild to moderate dementia expressed distinct preferences regarding physiotherapy sessions, communication, and family caregiver involvement. Addressing these preferences may improve adherence to and the effectiveness of exercise interventions. Additionally, the findings suggest a potential shift toward a more supervisory role for physiotherapists, rather than the traditional hands-on approach.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251349166"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276932","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":"Audio review as a measure of quality assurance and control of cognitive assessments in Alzheimer's disease studies: An experience from Japanese Trial-Ready Cohort Study.","authors":"Kenichiro Sato, Ryoko Ihara, Yoshiki Niimi, Kazushi Suzuki, Atsushi Iwata, Takeshi Iwatsubo","doi":"10.1177/25424823251349188","DOIUrl":"10.1177/25424823251349188","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials targeting preclinical Alzheimer's disease (AD) require accurate cognitive assessments to detect subtle changes over time. Audio review of assessment sessions has been proposed as a quality assurance (QA) and control (QC) measure, yet evidence regarding its effectiveness remains limited.</p><p><strong>Objective: </strong>We aim to investigate how audio review contributes to the QA/QC process.</p><p><strong>Methods: </strong>In the Japanese Trial-Ready Cohort (J-TRC) onsite study, 194 Preclinical Alzheimer's Cognitive Composite (PACC) sessions were audio-recorded and independently reviewed. Examiners were certified psychometrists who had undergone pre-training. Audio reviewers issued \"queries\" for scoring deviations warranting score amendments and \"comments\" for procedural deviations or recommended improvements. Mixed-effects models analyzed associations between the number of queries/comments and (1) cumulative PACC examination experience and (2) cumulative received feedback for individual examiners.</p><p><strong>Results: </strong>Of 194 reviewed sessions, 63.4% contained at least one query, and 84.5% included one or more comments. A higher cumulative number of PACC sessions by each examiner was associated with fewer queries and smaller score changes over time. Notably, the cumulative number of feedback reports was significantly associated with a lower number of comments, suggesting targeted feedback helped refine examiners' testing manner. However, cumulative feedback was not clearly linked to the frequency of scoring deviations (queries).</p><p><strong>Conclusions: </strong>These findings indicate that audio review can serve as an effective QA/QC measure by reducing non-adherence to assessment standards.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"9 ","pages":"25424823251349188"},"PeriodicalIF":2.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267977","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}