Alzheimer's Research & Therapy最新文献

{"title":"Structural brain improvements following individually tailored serious exergame-based training in mild neurocognitive disorders: exploratory randomized controlled trial.","authors":"Patrick Manser, Michael Rosio, André Schmidt, Lars Michels, Eling D de Bruin","doi":"10.1186/s13195-025-01835-2","DOIUrl":"10.1186/s13195-025-01835-2","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"190"},"PeriodicalIF":7.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herpesviruses, antiviral treatment, and the risk of dementia - systematic review and meta-analysis.","authors":"Nadia Jasmin Drinkall, Volkert Siersma, Richard Lathe, Gunhild Waldemar, Janet Janbek","doi":"10.1186/s13195-025-01838-z","DOIUrl":"10.1186/s13195-025-01838-z","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this systematic review and meta-analysis was to synthesize the evidence on the association between herpesviruses, antiviral treatment, and the risk of dementia. We also aimed to explore the impact of time between herpesviruses and dementia on the reported associations.</p><p><strong>Methods: </strong>PubMed and Web of Science were searched along with reference lists of the included studies. We included studies that looked at clinical episodes or serology (IgG/IgM) of herpes simplex virus type 1/2 (HSV1/2) and/or varicella zoster virus (VZV), antiviral treatment and incident dementia (all-cause dementia, Alzheimer's disease, and vascular dementia). Study results were pooled with random effect meta-analyses.</p><p><strong>Results: </strong>We included 32 studies. The pooled hazard ratio for all-cause dementia was 1.36 [95% CI: 1.01, 1.83] following a clinical episode of HSV1/2, and 1.12 [95% CI: 1.00, 1.25] following a clinical episode of VZV. The pooled estimate for all-cause dementia following antiviral treatment and VZV was 0.88 [95% CI: 0.81, 0.96].</p><p><strong>Conclusions: </strong>The present review of the scientific literature generally shows little evidence of an association between herpesviruses and risk of dementia. However, the review shows evidence of an association between antiviral treatment and a decreased risk of dementia. Because of considerable heterogeneity, future investigations could advantageously target certain subgroups.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"201"},"PeriodicalIF":7.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of electrophysiological rhythms and memory impairment in an Alzheimer's transgenic rat model.","authors":"Xiaoxiao Tao, Udaya Kumar, Miaomiao Wang, Kapil Manglani, Cansheng Zhu, Mychica R Jones, Alexander Bombino, Anatol Bragin, Gregory Cole, Keith Vossel, Jerome Engel, Sally A Frautschy, Lin Li","doi":"10.1186/s13195-025-01841-4","DOIUrl":"10.1186/s13195-025-01841-4","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is one of the most prevalent causes of dementia, characterized by progressive memory loss and cognitive decline. Abnormal electrophysiological patterns, especially interictal epileptiform discharges (IEDs) and high-frequency oscillations (HFOs), have been observed in mouse models of AD and are suggested to contribute to cognitive dysfunction. However, comprehensive evaluations of IEDs across different brain regions are limited, and their impact on cognitive performance and neuropathology remains unclear, particularly in more complex AD models with relevant comorbidities. To address this gap, our study aims to clarify how IEDs and HFOs contribute to cognitive decline and neuropathology in AD, potentially informing the development of new biomarkers for early detection.</p><p><strong>Methods: </strong>We investigate these effects in an AD (PS1/APP) rat model (FAD+) with coexisting hypertension-associated small vessel disease (SVD), as well as in their transgene-negative littermates (FAD-). We conducted behavioral experiments at 6, 8, and 11 months of animal age, alongside neural signal recordings at 8 and 11 months. AD pathology (neuritic plaques and hyperphosphorylated tau) and novel biomarkers (14-3-3γ) or biomarkers common to both disorders (neuropeptide Y, astrocyte and microglia) were evaluated at the end of the experiment.</p><p><strong>Results: </strong>Seizures were observed in three out of 14 FAD + rats. IED rates were significantly greater in FAD + rats compared to FAD- at all tested periods, correlating with changes in neuropathological biomarkers. Furthermore, coupling strength between IEDs and HFOs was significantly elevated in FAD + rats, especially during the later stages of disease progression. In addition, FAD + rats exhibited deficits in both learning and recall abilities at both ages, which correlated most strongly with increased IED-HFO coupling strength. No such correlation was observed in the FAD- group.</p><p><strong>Conclusion: </strong>Our findings suggest that pathological synchronization between IEDs and HFOs in the hippocampus, along with neuropathological changes in both the hippocampus and entorhinal cortex, may contribute to memory dysfunction in AD, highlighting a potential mechanistic link between epileptiform activity, AD biomarker changes, and cognitive decline.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"200"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early functional changes in lewy body dementia: roles of dynamics, locus coeruleus, and compensation.","authors":"Kristína Mitterová, Eva Výtvarová, Anežka Kovářová, Martin Lamoš, Jan Fousek, Irena Rektorová","doi":"10.1186/s13195-025-01828-1","DOIUrl":"https://doi.org/10.1186/s13195-025-01828-1","url":null,"abstract":"<p><p>Dementia with Lewy bodies (DLB) is marked by multidomain cognitive impairments, with fluctuations in cognition and alertness being among the most common clinical features. Disruptions in functional connectivity are thought to underlie these fluctuations, but it remains unclear whether such patterns are already present at prodromal stages. We investigated the presence of static and dynamic functional connectivity alterations and their contribution to the clinical phenotype of prodromal DLB, and explored their association with declining locus coeruleus integrity, while considering premorbid intelligence (a proxy for cognitive reserve) as a moderating factor. Three groups of participants on the prodromal spectrum were analyzed: 29 healthy controls, 58 cognitively normal subjects with core clinical features of prodromal DLB (CN-CCF), and 39 subjects with mild cognitive impairment due to Lewy body dementia (MCI-LB). Dynamic and static functional connectivity features were derived from resting-state source-reconstructed high-density EEG, and integrity of the right caudal locus coeruleus was quantified using neuromelanin-sensitive MRI. Robust analyses, such as PERMANOVA, Spearman correlations and general linear models were conducted to study the relationships. We observed a nonlinear trajectory of two functional connectivity metrics-temporal variability (fluidity) and connectedness (average node strength)-across symptom severity, especially in the delta frequency band. Both measures (F(2,123) = 1.86, p =.037; F(2,123) = 1.51, p =.023, respectively) were elevated in the intermediate severity groups-that is, in CN-CCF and possible MCI-LB (i.e., one core clinical feature)-and this was associated with better executive functioning after controlling for age and premorbid intelligence (rho = 0.26, p =.004; rho = 0.28, p =.002, respectively). Additionally, elevated fluidity (rho = - 0.34, p =.034) and average node strength (rho = - 0.37, p =.022) were also correlated with fewer fluctuations in alertness in subjects with MCI-LB. Fluidity was further associated with right caudal locus coeruleus integrity, particularly among individuals with lower premorbid intelligence (F(5,97) = 3.56, p =.005). Our findings indicate that increased dynamic reconfiguration and enhanced connectivity may serve compensatory functions in early DLB, helping temporarily preserve cognition. As DLB progresses, these mechanisms wane, with noradrenergic contributions more evident in individuals with lower cognitive reserve. Clinical trial number Not applicable.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"199"},"PeriodicalIF":7.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic syndrome and risk of incident all-cause dementia, Alzheimer's disease and vascular dementia: a systematic review and meta-analysis of longitudinal studies.","authors":"Danial Qureshi, Naomi E Allen, Elżbieta Kuźma, Thomas J Littlejohns","doi":"10.1186/s13195-025-01825-4","DOIUrl":"https://doi.org/10.1186/s13195-025-01825-4","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome (MetS) comprises several co-occurring vascular and cardiometabolic characteristics and might represent a novel modifiable risk factor for dementia, though findings remain inconsistent. To clarify this, we conducted a systematic review and meta-analysis of longitudinal studies investigating the association between MetS with risk of incident all-cause dementia, Alzheimer's disease and vascular dementia.</p><p><strong>Methods: </strong>We searched Medline, Embase and PsycINFO databases (from inception to Feb 19th, 2024) for longitudinal cohort studies investigating the association of MetS with incident all-cause dementia or key subtypes, including Alzheimer's, vascular, Lewy Body or other dementias. Random-effects models were used to estimate pooled hazard ratios (pHR) and 95% confidence intervals (CI). Risk of bias was assessed using the Quality Assessment Tool for Quantitative Studies.</p><p><strong>Results: </strong>Of 4,719 studies identified, fourteen studies met the eligibility criteria. These studies combined included 4,345,741 participants who were initially free of dementia. Pooled estimates showed that, compared to participants with no MetS, those with MetS had a significantly greater risk of incident all-cause dementia (4,307,830 participants, 27,708 cases, pHR: 1.12, 95% CI: 1.08-1.15, I² = 12.0%). No significant association was observed for incident Alzheimer's disease (4,109,436 participants, 14,890 cases, pHR: 0.91, 95% CI: 0.72-1.15, I²: 41.0%) or vascular dementia (4,109,436 participants, 2,642 cases, pHR: 1.40, 95% CI: 0.96-2.06, I²: 59.0%). Associations remained similar in subgroup analyses restricted to studies reporting results for those aged 65 + years: all-cause dementia (pHR: 1.08, 95% CI: 1.00-1.16, I²: 15.0%), Alzheimer's disease (pHR: 0.85, 95% CI: 0.65-1.11, I²: 0.0%), and vascular dementia (pHR: 1.55, 95% CI: 0.71-3.39, I²: 75.0%).</p><p><strong>Conclusions: </strong>Our findings demonstrate that MetS may be an important risk factor for developing dementia, and represent a potential target for prevention. Further studies are needed to understand the influence of MetS on specific dementia subtypes.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"198"},"PeriodicalIF":7.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term retrieval performance is associated with CA1 hippocampal volume in older adults and individuals at risk for dementia.","authors":"Claudia Bartels, Joy Tzu-Yueh Chen, Michael Belz, Renat Yakupov, Emrah Düzel, Wenzel Glanz, Falk Lüsebrink, Peter Dechent, Luca Kleineidam, Melina Stark, Annika Spottke, Marie Coenjaerts, Klaus Fließbach, Anja Schneider, Ayda Rostamzadeh, Frank Jessen, Björn H Schott, Jens Wiltfang, Ingo Frommann, Michael Wagner, Roberto Goya-Maldonado","doi":"10.1186/s13195-025-01833-4","DOIUrl":"https://doi.org/10.1186/s13195-025-01833-4","url":null,"abstract":"<p><strong>Background: </strong>Long-term retrieval (LTR) and accelerated long-term forgetting (ALF) paradigms might help differentiating individuals at increased dementia risk from healthy controls (HC).</p><p><strong>Objective: </strong>We investigated the utility of a LTR paradigm in discriminating subjective cognitive decline (SCD) from HC and its relationship to the CA1 body volume, a hippocampal structure pivotal to the memory circuitry.</p><p><strong>Methods: </strong>LTR was assessed via recall rates of the ADAS-cog word list and the FCSRT-IR free recall in 59 DELCODE study participants, including individuals with SCD and mild cognitive impairment (MCI), as well as HC, all of them DELCODE study participants. LTR performance was compared between groups and its discriminability between SCD and HC was assessed using ROC curve analysis. 32 SCD and HC participants had FreeSurfer-segmented MRI data, and hippocampal subfield volumes were correlated with LTR rates.</p><p><strong>Results: </strong>Only FCSRT-IR LTR rates sufficiently differentiated SCD from HC (AUC of 0.701; 95% CI 0.537-0.865). Moderate associations of the FCSRT-IR LTR rate with CA1 bodies in both hemispheres (left CA1 body r = 0.419, p = 0.017; right: r = 0.412, p = 0.019), in addition to the left C3 body were observed (r = 0.525, p = 0.002).</p><p><strong>Conclusions: </strong>LTR may constitute a potential indicator of memory circuitry integrity in older adults, which is also mirrored by its association with CA1 volume. Thus, assessment of LTR and associated neural circuits may help to better identify individuals at risk for future cognitive decline today indistinguishable from HC, ultimately paving the way for early intervention.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"195"},"PeriodicalIF":7.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between plasma and MRI biomarkers in dementia with lewy bodies.","authors":"Carmen Peña-Bautista, Katharina Bolsewig, Maria C Gonzalez, Nicholas J Ashton, Dag Aarsland, Henrik Zetterberg, Eric Westman, Olivier Bousiges, Frederic Blanc, Charlotte E Teunissen, Afina W Lemstra, Consuelo Cháfer-Pericás, Miguel Baquero, Daniel Ferreira","doi":"10.1186/s13195-025-01848-x","DOIUrl":"https://doi.org/10.1186/s13195-025-01848-x","url":null,"abstract":"<p><strong>Background: </strong>The diagnosis of Dementia with Lewy Bodies (DLB) is primarily based on clinical features. The main driver of DLB is alpha-synuclein-related pathology, but cerebrovascular disease (CVD) and Alzheimer's Disease (AD) co-pathologies are often found in patients with DLB. Fluid biomarkers and magnetic resonance imaging (MRI) can provide mechanistic and diagnostic information beyond clinical features. Therefore, the aim of this study was to investigate the association of plasma biomarkers (GFAP, NfL, Aβ42/40, pTau231, pTau181) with MRI markers of neurodegeneration and CVD in DLB and in patients with AD as a control group. We also evaluated the ability of biomarkers and clinical features to discriminate between DLB and AD.</p><p><strong>Methods: </strong>We included 134 patients from the European DLB consortium (DLB (n = 92) and AD (n = 43)) with plasma biomarkers determined with Simoa and MRI assessed with radiological scales for medial temporal lobe atrophy (MTA), global cortical atrophy scale - frontal subscale (GCA-F), posterior atrophy (PA), and cerebrovascular disease (Fazekas scale). Associations between plasma and MRI biomarkers were assessed with the Mann-Whitney U test, and group differences and the discrimination between DLB and AD were assessed with ANCOVA, Random Forest, and ROC analyses.</p><p><strong>Results: </strong>In DLB, plasma concentrations of GFAP and NfL were associated with MTA, GCA-F, and Fazekas scale; and the Aβ42/40 ratio was associated with PA and Fazekas. Most of these associations were not statistically significant in AD. Individually, plasma and MRI biomarkers had a limited ability to discriminate DLB from AD. Plasma biomarkers helped increase the low specificity of core clinical features from 68% up to 79%, keeping the high sensitivity of 90%.</p><p><strong>Conclusions: </strong>Plasma biomarkers of AD co-pathology, glial processes and unspecific neurodegeneration are associated with MRI biomarkers of atrophy and cerebrovascular disease in DLB patients. Plasma biomarkers increase the ability of core clinical features to discriminate between DLB and AD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"197"},"PeriodicalIF":7.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbial metabolite TMAO impairs cognitive function and induces hippocampal synaptic plasticity decline through modulation of GSK-3β activity.","authors":"Yachen Shi, Pan Wang, Jingyu Deng, Yunuo Chen, Feng Wang, Yan Han, Hui Wang, Yang Li, Xiangming Fang, Jiaojie Hui, Guangjun Xi","doi":"10.1186/s13195-025-01846-z","DOIUrl":"https://doi.org/10.1186/s13195-025-01846-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Growing evidence has suggested that elevated Trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite, are closely associated with brain aging and cognitive impairment. Glycogen synthase kinase-3 beta (GSK-3β) activity was depicted to be essential in regulating learning and memory. The current study examined the impact of TMAO on cognitive function in mild cognitive impairment (MCI) patients and rat models while exploring the mechanisms regulating the TMAO-induced GSK-3β signaling.</p><p><strong>Methods: </strong>This study recruited 115 MCI patients and 128 healthy controls. All participants underwent neuropsychological assessments. Fasting plasma TMAO was measured using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. The study also explored whether the GSK-3β signaling was involved in cognitive and function deficits linked with elevated TMAO in rat models.</p><p><strong>Results: </strong>Our results indicated that TMAO plasma levels were elevated in MCI patients compared to healthy controls, depicting a significant association with potential MCI risk. Furthermore, chronic exposure to choline considerably impacted spatial cognitive performance in the Morris water maze task. This reduced the phosphorylation of Ser9 of GSK-3β and the synaptic plasticity-related proteins within the hippocampus, which could be restored by inhibiting TMAO with ABS. In addition, inhibition of GSK-3β by SB216763 significantly prevented the TMAO-induced synaptic damage while decreasing the membrane level of GluA1 and improving hippocampal learning and memory.</p><p><strong>Discussion: </strong>These results indicate that TMAO can induce hippocampal-dependent learning and memory ability impairment with deficits in synaptic plasticity by regulating the GSK-3β activity.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"196"},"PeriodicalIF":7.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing timing and cost-effective use of plasma biomarkers in Alzheimer's disease.","authors":"Hsin-I Chang, Mi-Chia Ma, Kuo-Lun Huang, Chung-Gue Huang, Shu-Hua Huang, Chi-Wei Huang, Kun-Ju Lin, Chiung-Chih Chang","doi":"10.1186/s13195-025-01851-2","DOIUrl":"10.1186/s13195-025-01851-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Early and cost-effective identification of amyloid positivity is crucial for Alzheimer's disease (AD) diagnosis. While amyloid PET is the gold standard, plasma biomarkers such as phosphorylated tau 217 (pTau217) provide a potential alternative. This study evaluates the diagnostic accuracy of a combined-panel approach using machine learning models and evaluated the biomarker significance.</p><p><strong>Methods: </strong>We enrolled 371 participants, including AD (n = 143), non-AD (n = 159), and cognitively unimpaired (CU, n = 69) controls. Combined panels of pTau217, pTau181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), Aβ42/40, and total tau were measured prior to the amyloid PET scan. The multiclass logistic (LR) regression, support vector machines, decision trees, and random forests (RF)-were applied to classify amyloid positivity (A+) at all stages or at early clinical stages (1-3). In AD, we tested whether the biomarker may define the clinical stagings.</p><p><strong>Results: </strong>When benchmarked against amyloid PET, plasma biomarker-based stratification achieves an optimal balance between diagnostic accuracy and cost-effectiveness. The multi-class LR performed equivalently with RF model in identifying A+. The combined plasma panel reached an > 92% accuracy in identifying A+, with performance increasing to 93.4% at early clinical stages. We ranked the importance of individual biomarkers and pTau217 alone achieved comparable accuracy (> 90%) and was the top-ranked biomarker in the LR or RF model. NFL and GFAP correlated significantly with Mini-Mental State Examination; however, these plasma biomarkers did not enhance clinical staging stratification.</p><p><strong>Discussion: </strong>The use of multiclass LR model enhances amyloid classification, particularly at earlier clinical stages. While the combined-panel approach is most accurate, pTau217 alone provides a cost-effective alternative for screening. These findings support the integration of plasma biomarkers and ML into clinical workflows for early detection and patient stratification.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"194"},"PeriodicalIF":7.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial delivery of simvastatin by LRP1-targeted nanoparticles ameliorates pathogenesis of alzheimer's disease in a mouse model.","authors":"Ting-Ting Pan, Yan-Yun Sun, Yi-Fan Shi, Mei Zhao, Naveed Ullah Khan, Hai-Yan Chen, Wen-Li Ji, Jie Li, Liang Han, Quan-Hong Ma","doi":"10.1186/s13195-025-01840-5","DOIUrl":"10.1186/s13195-025-01840-5","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"193"},"PeriodicalIF":7.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}