Alzheimer's Research & Therapy最新文献

{"title":"Protein co-aggregates of dense core amyloid plaques and CSF differ in rapidly progressive Alzheimer's disease and slower sporadic Alzheimer's disease.","authors":"Gurkan Bebek, Masaru Miyagi, Xinglong Wang, Brian S Appleby, James B Leverenz, Jagan A Pillai","doi":"10.1186/s13195-025-01767-x","DOIUrl":"https://doi.org/10.1186/s13195-025-01767-x","url":null,"abstract":"<p><strong>Background: </strong>The rapidly progressive phenotype of Alzheimer's disease (rpAD) remains a rare and less-studied entity. Therefore, the replication of key results from the rpAD brain and cerebrospinal fluid (CSF) is lacking.</p><p><strong>Methods: </strong>A label-free quantitative LC-MS/MS analysis of proteins co-aggregating with core-amyloid <math><mi>β</mi></math> plaques in fresh frozen tissue (FFT) from medial temporal regions of rpAD ( <math><mrow><mi>n</mi> <mo>=</mo> <mn>8</mn></mrow> </math> ) neuropathologically characterized at the National Prion Disease Pathology Surveillance Center (NPDPSC), compared with microdissected amyloid plaques from formalin-fixed, paraffin-embedded (FFPE) tissue blocks from patients with rpAD ( <math><mrow><mi>n</mi> <mo>=</mo> <mn>22</mn></mrow> </math> ) previously published from the NPDPSC cohort, was performed. Matched rpAD CSF from the FFT cases were compared to a previously published proteomic evaluation of CSF in the AD subtype with rapid progression.</p><p><strong>Results: </strong>A total of 1841 proteins were characterized in the FFT study, of which 463 were consistently identified in every rpAD patient analyzed. One thousand two hundred eighty-three proteins were shared between the FFT and the prior FFPE study. FFT offered a more comprehensive proteomic profile than the prior FFPE study and prominently included the immune system pathways. Thirty-five proteins were shared in the FFT brain tissue, matched CSF from the same subjects, in which biological processes related to immune response were again notable. These results were validated against prior published proteomic CSF AD data with a faster rate of progression to identify the top 5 potential protein biomarkers of rapid progression in AD CSF.</p><p><strong>Conclusions: </strong>These results support a distinct immune-related proteomic profile in both the brain and the CSF that can be explored as potential biomarkers in the future for the clinical diagnosis of rpAD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"118"},"PeriodicalIF":7.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on the perspectives of people affected by dementia with Lewy bodies: a scoping review.","authors":"Paula Sinead Donnelly, Aoife Sweeney, Anthony P Passmore, Noleen K McCorry, Joseph P M Kane","doi":"10.1186/s13195-025-01760-4","DOIUrl":"https://doi.org/10.1186/s13195-025-01760-4","url":null,"abstract":"<p><strong>Background: </strong>Dementia with Lewy bodies (DLB) is associated with specific challenges, including heterogeneity in clinical presentation and a less favourable prognosis relative to other dementia subtypes. These challenges necessitate person-centred care informed by the perspectives of those affected by DLB. This scoping review aimed to map the extent, type, and nature of research focusing on the perspectives of individuals with DLB and their care partners.</p><p><strong>Methods and results: </strong>We searched six databases and two grey literature sources to identify all types of work providing information on the perspectives of individuals with DLB and/or their care partners. Two reviewers independently applied study selection criteria. Data from eligible articles were extracted, charted, and summarised using descriptive numerical analysis and basic qualitative content analysis. The review included 140 sources, of which 89.3% were research articles. Excluding non-structured reflections and commentary articles (n = 4), 68.4% of sources were quantitative and 65.4% were cross-sectional. The most common method of collecting perspective data was standardised measures assessing multidimensional concepts, such as caregiver burden. In total, 13 topics were identified, with 'emotional and psychological well-being' (n = 64) being the most widely investigated. There was a significant gap before the next most common topic: 'perspectives related to the symptom and illness experience' (n = 34).</p><p><strong>Conclusion: </strong>While a range of methods was identified in this review, the evidence base is characterised by a predominance of standardised measures, with comparatively less use of qualitative approaches or non-standardised tools incorporating bespoke questions tailored to the study population. There was a disproportionate focus on specific topics, leading to research gaps. We recommend exploring novel methods to systematically capture perspectives in DLB cohorts, particularly on topics of highest priority to those affected.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"117"},"PeriodicalIF":7.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the introduction of anti-amyloid therapy in Europe: a position statement by individual members of the EADC.","authors":"Kristian S Frederiksen, Mercé Boada, Bruno Dubois, Sebastiaan Engelborghs, Giovanni B Frisoni, Jean Georges, Jakub Hort, Linus Jönsson, Milica G Kramberger, Pierre-Jean Ousset, Nikolaos Scarmeas, Reinhold Schmidt, Jonathan M Schott, Luiza Spiro, Gunhild Waldemar, Bengt Winblad, Frank Jessen, Lutz Frölich","doi":"10.1186/s13195-025-01766-y","DOIUrl":"10.1186/s13195-025-01766-y","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-amyloid antibodies for the treatment of Alzheimer´s disease (AD) are currently being evaluated for approval and reimbursement in Europe. An approval brings opportunities, but also challenges to health care systems across Europe. The objective of this position paper is to provide guidance from experts in the field in terms of navigating implementation.</p><p><strong>Methods: </strong>Members of the European Alzheimer's Disease Consortium and a representative of Alzheimer Europe convened to formulate recommendations covering key areas related to the possible implementation of anti-amyloid antibodies in AD through online discussions and 2 rounds of online voting with an 80% threshold for a position to be accepted.</p><p><strong>Results: </strong>In total, 24 recommendations were developed covering the research landscape and priorities within research in AD following a possible approval, potential impact on health care systems and diagnostic pathways, and communication to patients about anti-amyloid antibodies. Anti-amyloid antibodies are regarded as a substantial innovation with an important clinical impact. In addition, however, new compounds with other mechanisms of action and/or route of administration are also needed. Approval of new treatments will require changes to existing patient pathways and real-world data needs to be generated.</p><p><strong>Conclusion: </strong>Comprehensive guidance is provided on the potential implementation of anti-amyloid antibody therapies in Europe following possible approval. Emphasis is placed on the necessity of regularly updating recommendations as new evidence emerges in the coming years.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"116"},"PeriodicalIF":7.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141374","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":"Novel fully human high-affinity anti-TREM2 antibody shows efficacy in clinically relevant Alzheimer´s mouse model.","authors":"Markus Kraller, Julia Faßbender, Ammar Jabali, Joseph Kroeger, Barbara Fink, Bastian Popper, Martin Ungerer, Miriam A Christlmeier","doi":"10.1186/s13195-025-01759-x","DOIUrl":"10.1186/s13195-025-01759-x","url":null,"abstract":"<p><strong>Background: </strong>New drugs to treat Alzheimer´s disease (AD) are urgently needed. Human triggering receptor expressed on myeloid cells 2 (hTREM2) is a validated drug target which is genetically associated with AD. Existing anti-hTREM2 antibodies were raised in animal immune systems, and subsequently humanized, which may incur immunological complications upon repeated preventive or therapeutic applications in vivo in AD patients. In addition, anti-hTREM2 antibodies should be optimized for both, efficacy and safety.</p><p><strong>Methods: </strong>A novel fully human monoclonal brain-targeting anti-hTREM2 antibody M07-TFN was created. Binding affinities, cell viabilities, and agonist potencies were investigated on rhTREM2 and in human microglia. Transcytosis assays modeled blood-brain barrier translocation (BBB). Behavior tests were carried out in 5 × familiar AD (5xFAD) mice of both genders, to test for brain function and cognition as well as hippocampus-dependent spatial memory using the Barnes maze. In addition, amyloid plaque formation was determined on brain sections at the end of the study.</p><p><strong>Results: </strong>M07-TFN showed higher binding affinities and stronger activation of hTREM2 signaling than all previously described anti-hTREM2 antibodies. p-Syk activation was increased 30-fold in hTREM2-overexpressing HEK293 cells and fourfold in human microglia cells compared to baseline. Human microglia viability significantly improved after stress testing. M07-TFN showed strong BBB translocation in a human BBB model, and exerted cross-reactivity to the mouse TREM2 stalk region, which allowed us to investigate M07-TFN directly in an AD mouse model. In 5xFAD mice, M07-TFN resulted in improved novel object location and better spatial orientation and memory, and significantly reduced plaque load. Additional safety investigations in mice showed no negative effects on blood cells or major organs.</p><p><strong>Conclusion: </strong>Compared to existing humanized anti-hTREM2 antibodies that have been investigated in clinical trials, M07-TFN showed best-in-class affinities and agonist potencies. Being a fully human anti-hTREM2 antibody, M07-TFN holds the promise of reduced immunogenicity for use in human patients.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"114"},"PeriodicalIF":7.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126362","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":"Correction: Abdominal obesity and the risk of young-onset dementia in women: a nationwide cohort study.","authors":"Ye Seul Yang, Kyungdo Han, Dae Young Cheon, Minwoo Lee","doi":"10.1186/s13195-025-01758-y","DOIUrl":"10.1186/s13195-025-01758-y","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"113"},"PeriodicalIF":7.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126150","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":"Influence of co-pathology on CSF and plasma synaptic markers SNAP25 and VAMP2 in Alzheimer's disease and Parkinson's disease.","authors":"Lorenzo Gaetani, Giovanni Bellomo, Davide Chiasserini, Charlotte De Rocker, Julie Goossens, Federico Paolini Paoletti, Eugeen Vanmechelen, Lucilla Parnetti","doi":"10.1186/s13195-025-01762-2","DOIUrl":"10.1186/s13195-025-01762-2","url":null,"abstract":"<p><strong>Background: </strong>Synaptic dysfunction is a relevant feature of Alzheimer's disease (AD) and Parkinson's disease (PD) and can be quantified through the measurement of cerebrospinal fluid (CSF) synaptic markers, such as the presynaptic proteins synaptosomal-associated protein 25 kDa (SNAP25) and vesicle-associated membrane protein 2 (VAMP2). Plasma-based assays for synaptic markers are also emerging. In neurodegenerative diseases, synaptic dysfunction can be directly driven by proteinopathies such as amyloidosis (A), tauopathy (T), and α-synucleinopathy (S), which in turn can be detected via CSF biomarkers. This observational study aimed to: (i) evaluate the concordance of SNAP25 and VAMP2 in CSF and plasma; (ii) compare SNAP25 and VAMP2 concentrations in CSF and plasma across AD, PD, and control groups; (iii) examine the impact on synaptic markers concentration of CSF α-synuclein seed amplification assay (αS-SAA) positivity (S+) in AD, and (iv) of CSF amyloid/tau (A+/T+) positivity in PD.</p><p><strong>Methods: </strong>We included 80 AD patients (preclinical, mild cognitive impairment [MCI], and dementia stages), 47 PD patients, and 41 controls with other neurological diseases (OND) and known CSF A/T/S profiles. All AD and 5/47 PD patients were CSF A+/T+, while 26/80 AD and all PD patients were CSF S+. All OND had a non-A+/T + and a S - profile. SNAP25 and VAMP2 concentrations in CSF and plasma were measured using Simoa-based immunoassays.</p><p><strong>Results: </strong>CSF and plasma SNAP25 were positively correlated, but no correlation was observed for VAMP2 in these matrices. CSF and plasma SNAP25 and CSF VAMP2 were higher in AD compared to PD and OND. Synaptic markers were elevated in preclinical AD and remained stable across MCI-AD and AD dementia stages. AD patients with CSF αS-SAA positivity showed no significant difference in synaptic markers compared to those without CSF αS-SAA positivity, independent of clinical stage. In PD, A+/T + patients had higher CSF and plasma SNAP25 (132.3 ± 41.6; 1.9 ± 0.5 pg/mL) compared to non-A+/T + PD (105.4 ± 34.2; 1.3 ± 0.3 pg/mL) (p < 0.001 and p < 0.01, respectively).</p><p><strong>Conclusions: </strong>SNAP25 reliably serves as a marker of synaptic injury when measured in both CSF and plasma, whereas VAMP2 demonstrates reliability exclusively in CSF. Both markers are primarily influenced by AD pathology and remain unaffected by α-synucleinopathy, suggesting their potential in detecting AD-related synaptic dysfunction.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"115"},"PeriodicalIF":7.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126205","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":"Development of a Japanese polygenic risk score model for amyloid-β PET imaging in Alzheimer's disease.","authors":"Misato Kaishima, Junichi Ito, Kentaro Takahashi, Kenji Tai, Junro Kuromitsu, Shogyoku Bun, Daisuke Ito","doi":"10.1186/s13195-025-01754-2","DOIUrl":"10.1186/s13195-025-01754-2","url":null,"abstract":"<p><strong>Background: </strong>The use of polygenic risk scores (PRS) for predicting disease risk in Japanese populations, particularly for dementia and related phenotypes, remains markedly unexplored. The aim of this study was to bridge this gap by developing a novel PRS model designed to predict amyloid-β (Aβ) deposition utilizing positron emission tomography (PET) imaging data from a Japanese cohort.</p><p><strong>Methods: </strong>Using the polygenic risk score-continuous shrinkage (PRS-CS) algorithm, we calculated PRS based on significant single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) in this population. We applied a PRS calculation approach informed by Japanese genome-wide association studies (GWAS) summary statistics into a Japanese dementia cohort from Keio University.</p><p><strong>Results: </strong>Our findings revealed that a p-value threshold of pT < 0.1 optimally enhanced the predictive capability of the Japanese Aβ PET positivity risk model. Moreover, we demonstrated that distinguishing between the counts of APOE2 and APOE4 alleles in our calculations significantly elevated model performance, achieving an area under the curve (AUC) of 0.759. Remarkably, this predictive accuracy remained robust even when the pT was adjusted to be < 1.0 × 10^- 5, maintaining an AUC of 0.735. This study validated the efficacy of the model in identifying individuals with a increased risk of amyloid pathology.</p><p><strong>Conclusions: </strong>These findings highlight the potential of PRS as a noninvasive tool for early detection and risk stratification of AD, which could lead to enhanced clinical applications and interventions.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"112"},"PeriodicalIF":7.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126259","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":"Diagnostic performance of actigraphy in Alzheimer's disease using a machine learning classifier - a cross-sectional memory clinic study.","authors":"Mathias Holsey Gramkow, Andreas Brink-Kjær, Frederikke Kragh Clemmensen, Nikolai Sulkjær Sjælland, Gunhild Waldemar, Poul Jennum, Steen Gregers Hasselbalch, Kristian Steen Frederiksen","doi":"10.1186/s13195-025-01751-5","DOIUrl":"https://doi.org/10.1186/s13195-025-01751-5","url":null,"abstract":"<p><strong>Background: </strong>Movement patterns, activity levels and circadian rhythm are altered in Alzheimer's disease (AD) and can be assessed by actigraphy using wearable sensors. We aimed to determine the diagnostic performance of actigraphy in AD in a memory clinic population by using a machine-learning classifier.</p><p><strong>Methods: </strong>In our single-center cross-sectional study, 70 patients with AD (MCI-moderate dementia), dementia with Lewy bodies (DLB) (N = 29) and cerebrovascular disease (CVD) (N = 23), and 48 elderly healthy controls were included. Participants underwent actigraphy at home using two body-worn sensors (SENS Motion^®) for 1 week. We derived movement patterns (walking, running, resting, etc.) from raw accelerometry data using a proprietary algorithm. By evaluating the movement patterns during day and nighttime, we calculated 510 activity-related features, including robustness and fragmentation of the circadian rhythm. These features were used to train a machine learning (ML) classifier using logistic regression. We evaluated the performance of our classifier by assessing the accuracy and precision of predictions.</p><p><strong>Results: </strong>We found that movement patterns as well as the robustness and fragmentation of the circadian rhythm differed significantly between groups. During the daytime, patients with AD performed less moderate activity and walked less than the healthy group. While we achieved a modest accuracy of 68.8% for differentiating AD and healthy, the performance was highest (accuracy: 80-89%; precision: 69-84%) when ML was applied to actigraphy data to differentiate dementia etiologies (AD vs. DLB + AD vs. CVD).</p><p><strong>Conclusion: </strong>Actigraphy accurately identifies different dementia etiologies and could serve as a supplement to diagnostic investigations in patients with suspected AD for differential diagnostic purposes.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"111"},"PeriodicalIF":7.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Short‑term variability of Alzheimer's disease plasma biomarkers in a mixed memory clinic cohort.","authors":"Frederikke Kragh Clemmensen, Mathias Holsey Gramkow, Anja Hviid Simonsen, Nicholas J Ashton, Hanna Huber, Kaj Blennow, Henrik Zetterberg, Gunhild Waldemar, Steen Gregers Hasselbalch, Kristian Steen Frederiksen","doi":"10.1186/s13195-025-01746-2","DOIUrl":"10.1186/s13195-025-01746-2","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"110"},"PeriodicalIF":7.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118558","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":"Cannabidiol as a multifaceted therapeutic agent: mitigating Alzheimer's disease pathology and enhancing cognitive function.","authors":"Iu Raïch, Jaume Lillo, Joan Biel Rebassa, Christian Griñán-Ferré, Aina Bellver-Sanchis, Irene Reyes-Resina, Rafael Franco, Mercè Pallàs, Gemma Navarro","doi":"10.1186/s13195-025-01756-0","DOIUrl":"10.1186/s13195-025-01756-0","url":null,"abstract":"<p><strong>Background: </strong>Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has garnered significant interest due to its non-psychoactive nature and diverse receptor interactions.</p><p><strong>Methods: </strong>This study employs in vitro and in vivo methodologies to validate CBD's potential as a treatment for Alzheimer's disease (AD) by addressing key hallmarks of the condition and promoting neuroprotective effects on spatial memory.</p><p><strong>Results: </strong>Our findings demonstrate CBD's ability to decrease pTau and Aβ aggregation and to mitigate their axonal transport between cortical and hippocampal neurons. Moreover, CBD treatment was shown to reduce neuroinflammation, as CBD was able to skew microglia towards a neuroprotective M2 phenotype while attenuating proinflammatory cytokine release in the 5xFAD AD mouse model. Notably, daily CBD injections (10 mg/Kg) for 28 days in 5xFAD mice resulted in significant improvements in both short- and long-term spatial memory. The study also reveals CBD's capacity to partially revert neurite formation loss induced by Aβ, Tau, and pTau proteins, suggesting a potential role in promoting neuronal plasticity. Additionally, CBD treatment led to a reduction in reactive oxygen species (ROS) formation and increased neuronal viability in the presence of AD-associated protein aggregates.</p><p><strong>Conclusions: </strong>These multifaceted effects of CBD, ranging from molecular-level modulation to behavioral improvements, underscore its potential as a comprehensive therapeutic approach for AD. The findings not only support CBD's neuroprotective properties but also highlight its ability to target multiple pathological processes simultaneously, offering a promising avenue for future AD treatment strategies.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"109"},"PeriodicalIF":7.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109433","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}