Journal of Alzheimer's Disease最新文献

{"title":"Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers.","authors":"Alzbeta Katonova, Ross Andel, Vanesa Jurasova, Katerina Veverova, Francesco Angelucci, Vaclav Matoska, Jakub Hort","doi":"10.1177/13872877251326199","DOIUrl":"10.1177/13872877251326199","url":null,"abstract":"<p><p>Background<i>KLOTHO</i>-VS heterozygosity (<i>KL</i>-VSHET) and soluble α-Klotho (sαKl) protein interfere with Alzheimer's disease (AD) pathophysiology, but the specific relationships remain unclear. This study explored these associations across the AD continuum, focusing on core AD biomarkers and markers of neurodegeneration, neuroinflammation, and synaptic dysfunction.ObjectiveWe investigated whether 1) <i>KL</i>-VSHET is associated with lower AD biomarker burden (Aβ₄₂, Aβ_42/40 ratio, P-tau181, T-tau) and neurodegeneration (NfL); 2) sαKl relates to AD biomarkers, neurodegeneration (NfL), neuroinflammation (GFAP), and synaptic dysfunction (Ng); 3) associations vary by <i>APOE</i> ε4 status and clinical subgroup.MethodsParticipants (n = 223) were categorized as cognitively healthy (n = 38), aMCI-AD (n = 94), and AD dementia (n = 91). <i>KLOTHO</i> genotyping was available for 128 participants; 138 had cerebrospinal fluid (CSF) and serum sαKl measurements; and 42 had both. Multiple linear regression evaluated associations between <i>KL</i>-VSHET, sαKl levels, and biomarkers, stratified by <i>APOE</i> ε4 status and clinical subgroup.ResultsOverall, the associations between <i>KL</i>-VSHET and higher CSF Aβ₄₂ and Aβ_42/40 ratio were non-significant (<i>p</i>s ≥ 0.059) except when restricted to <i>APOE</i> ε4 carriers only (β = 0.11, <i>p </i>= 0.008 and β = 0.16, <i>p </i>= 0.033, respectively). Within clinical subgroups, <i>KL</i>-VSHET was positively associated with Aβ_42/40 ratio only in aMCI-AD (β = 0.23, <i>p </i>= 0.034). No significant associations were observed between <i>KL</i>-VSHET and tau biomarkers or NfL. For sαKl, associations with biomarkers were non-significant except for a negative association of serum sαKl with P-tau181 in aMCI-AD (β = -0.25, p = 0.036) and a positive association with Aβ_42/40 ratio in <i>APOE</i> ε4 non-carriers (β = 0.24 p = 0.047).Conclusions<i>KL</i>-VSHET may help protect against amyloid pathology, particularly in the presence of <i>APOE</i> ε4, and regardless of <i>APOE</i> status in aMCI-AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"159-171"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered tear fluid protein expression in persons with mild Alzheimer's disease in proteins involved in oxidative stress, protein synthesis, and energy metabolism.","authors":"Virve Kärkkäinen, Toni Saari, Sanna Hannonen, Minna Rusanen, Juha-Matti Lehtola, Hannu Uusitalo, Ville Leinonen, Bernd Thiede, Kai Kaarniranta, Anne M Koivisto, Tor P Utheim","doi":"10.1177/13872877251326868","DOIUrl":"10.1177/13872877251326868","url":null,"abstract":"<p><p>BackgroundTear fluid (TF) is a protein-rich solution that reflects pathophysiological changes in Alzheimer's disease (AD).ObjectiveIn this study, we examined whether TF proteins were differently expressed in persons with mild AD dementia compared to cognitively healthy controls (CO).MethodsWe analyzed data from 53 study participants including 34 CO (mean age, 71 years; Mini-Mental State Examination [MMSE] score, 28.9 ± 1.4), and 19 patients with AD (Clinical Dementia Rating, 0.5-1; mean age, 72 years; MMSE score, 23.8 ± 2.8). All participants underwent cognitive testing, as well as neurological and ophthalmological examinations. TF was collected using Schirmer strips, and TF protein content was evaluated using mass spectrometry-based proteomics and label-free quantification.ResultsWe found that 16 proteins exhibited significantly upregulated expression in the AD group compared to the CO group (<i>p </i>≤ 0.05). These proteins were NP1L4, BBOX1, CYTC, RNAS4, PCD, RNT2, AL1A3, SYSC, TPIS, CLH1, PGAM1, EIF3L, 5NTC, HNRNPA2B1, PYGL, and ERO1α. No proteins were significantly downregulated in the AD group compared to the CO group.ConclusionsOur results support the hypothesis that TF is a potential source of biomarkers for AD. Part of those proteins with altered expression have previously linked to increased oxidative stress, changed protein synthesis, and disturbed regulation of energy metabolism related to AD or neurodegenerative disease. The present results indicate the value of continued investigation of TF proteins in AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"292-301"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Housing damage and forgetfulness following the 2024 Noto Peninsula earthquake, Japan.","authors":"Moeko Noguchi-Shinohara, Taro Ozaki, Yuta Usui, Syutaro Shibata, Ayano Shima, Junji Komatsu, Kenjiro Ono","doi":"10.1177/13872877251335005","DOIUrl":"https://doi.org/10.1177/13872877251335005","url":null,"abstract":"<p><p>On January 1, 2024, a major earthquake struck Japan's Noto Peninsula. From 2021 to 2023, we conducted a baseline survey. Four months after the disaster, we conducted a follow-up survey to investigate the relationship between house damage and forgetfulness in older adults without dementia. A total of 923 individuals were included. Among the respondents, 32.2% and 33.8% reported as suffered major house damages and increased forgetfulness, respectively. Multivariate analysis revealed major house damage was significantly associated with self-reported forgetfulness, which are partly mediated through sleep disturbance and sedentary behavior in the cognitively unimpaired and mild cognitive impairment groups, respectively.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251335005"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-targeted Mendelian randomization analysis combined with transcriptome sequencing to explore the molecular mechanisms associated with cognitive impairment.","authors":"Xixi Wu, Qingyan Yang, Yudi Xie, Lingfeng Xia, Jiatao Li, Wenting An, Xiao Lu","doi":"10.1177/13872877251335891","DOIUrl":"https://doi.org/10.1177/13872877251335891","url":null,"abstract":"<p><p>BackgroundCurrent therapies for cognitive impairment, including Alzheimer's disease (AD) and mild cognitive impairment, are limited by a lack of universal treatment and adverse effects associated with polypharmacy. Investigating genetic and molecular mechanisms underlying cognitive decline is critical for the development of targeted therapeutics.ObjectiveTo identify causal genes and potential therapeutic targets for cognitive impairment through integrative genomic analyses.MethodsGenome-wide association study data on cognitive impairment were combined with the expression quantitative trait loci (eQTL) data from the eQTLGen consortium. Mendelian randomization (MR) and colocalization analyses were employed to infer causal relationships. Gene Set Enrichment Analysis and Gene Set Variation Analysis evaluated the pathway and functional differences. Immune cell infiltration patterns and the immunometabolic pathways were assessed, followed by drug target prediction.ResultsMR analysis identified seven gene-eQTL pairs significantly associated with cognitive impairment. SMR colocalization prioritized three key genes: HNMT (histamine metabolism), TNFSF8 (inflammatory signaling), and S1PR5 (sphingolipid signaling). HNMT, TNFSF8, and S1PR5 had 39, 24, and 30 predicted targeted drugs, respectively, including arsenic trioxide, aspirin, and immunomodulators.ConclusionsThis study implicates HNMT, TNFSF8, and S1PR5 as potential therapeutic targets for cognitive impairment. Further validation is required to confirm their clinical relevance.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251335891"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between cerebral small vessel disease and reduced forced vital capacity and expiratory volume in a general healthy Swedish elder population study-Good Aging in Skåne.","authors":"Sölve Elmståhl, Katarina Ellström, Tomas Månsson, Rani Basna, Arkadiusz Siennicki-Lantz, Kasim Abul-Kasim","doi":"10.1177/13872877251333793","DOIUrl":"https://doi.org/10.1177/13872877251333793","url":null,"abstract":"<p><p>BackgroundCerebral small vessel disease (CSVD) is one of the most important causes of cognitive decline. Only a few previous studies have evaluated lung function measures in relation to brain neuropathological changes, and even less studies on specific lesions and areas that could shed light on mechanisms of CSVD.ObjectiveThe aim was to study the association between lung function and CSVD in the general elder population.Methods379 participants, aged 72-87 years from the general population study 'Good Aging in Skåne study (GÅS)'were investigated with a 3 T MRI brain examination and spirometry. Z-scores of FEV₁ and FVC were calculated using the GLI 2012 equations. Age-adjusted associations between white matter hyperintensities (WMH), medial temporal lobe atrophy (MTA), lacunar infarction, cerebral atrophies and cerebral microbleeds and lung function were calculated and stratified for sex.ResultsDecreased FEV₁ and FVC z-scores below ≤ -1.0 were both associated with increased risk of WMI and global cortical atrophy. Decreased FVC z-scores were also associated with MTA and lacunar infarction in women and precuneus atrophy in men. The associations for WMH, MTA and lacunar infarctions and higher STRIVE score were noted among women, but not among men. FEV₁ z scores were not related to diabetes, coronary artery disease or stroke.ConclusionsLower lung function was associated to MRI markers of CSVD in this general healthy population, particularly with WMH, especially for women. Although possible shared risk factors exist between lung and heart disease, lung function should be recognized in future studies on CSVD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333793"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the associations between tau and mental orientation among cognitively unimpaired individuals.","authors":"Mark A Dubbelman, Uri Elias, Phebe Palmer, Amnon Dafni-Merom, Lidor Gazit, Onyinye J Udeogu, Sharon Wang, Kathryn V Papp, Rebecca E Amariglio, Shahar Arzy, Gad A Marshall","doi":"10.1177/13872877251334781","DOIUrl":"https://doi.org/10.1177/13872877251334781","url":null,"abstract":"<p><p>BackgroundImpairments in orientation in space, time, and person occur frequently in Alzheimer's disease (AD) dementia. Subtle changes in orientation may arise in preclinical and prodromal disease stages. Thus, assessing orientation may help identify those on a trajectory toward AD dementia.ObjectiveTo investigate how orientation, measured using a novel artificial intelligence-based paradigm, relates to AD biomarkers (amyloid and tau) in cognitively unimpaired older adults.MethodsUsing an automated chatbot, 53 cognitively unimpaired participants (74.0 ± 5.5 years; 60% female) provided details about memories and relationships, recognition of historical event dates, and geographical locations. These details were then used to assess orientation to space, time, and person. For each domain separately, orientation accuracy was calculated by dividing the number of correct responses by response time. All participants underwent Pittsburgh compound-B (amyloid) and flortaucipir (tau) positron emission tomography. We analyzed the relationship between performance on the three orientation domains and retrosplenial, precuneus, neocortical, and medial temporal tau, and global amyloid.ResultsHigher retrosplenial and precuneus tau burden were associated with worse temporal orientation (β = -0.32, 95% confidence interval [95%CI] = [-0.59, -0.05] and β = -0.29, 95%CI = [-0.57, -0.01], respectively). Spatial or social orientation were not associated with amyloid or tau.ConclusionsThese results suggest that impaired temporal orientation is related to AD pathological processes, even before the onset of overt cognitive impairment, and may infer a role for personalized assessment of orientation in early diagnosis of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251334781"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel finding relates to the involvement of ATF3/DOCK8 in Alzheimer's disease pathogenesis.","authors":"Wenqiang Zhang, Fei Teng, Xifa Lan, Peihui Liu, Aiming Wang, Fan Zhang, Zhiqiang Cui, Jingwei Guan, Xiaohong Sun","doi":"10.1177/13872877251336266","DOIUrl":"https://doi.org/10.1177/13872877251336266","url":null,"abstract":"<p><p>BackgroundThe involvement of microglia is likely to be pivotal in the pathogenesis of Alzheimer's disease (AD) by modulating the deposition of amyloid-β (Aβ) plaques. The deletion of Dedicator of cytokinesis 8 (DOCK8) has a protective effect in mouse with neurodegenerative diseases.ObjectiveTo explore the underlying mechanism of DOCK8 in AD.MethodsIn present study, we first the detected the expression of DOCK8 in the hippocampal tissue of APP/PS1 mice. Then, the expression of DOCK8 was knocked down in the hippocampal tissue of APP/PS1 mice, and the effects of DOCK8 down-regulation on cognitive function, the microglia migration around Aβ plaques, and the cell division cycle 42 (Cdc42)/p38 mitogen-activated protein kinase (MAPK) signaling pathway were detected. Next, the effects of DOCK8 knockdown on Aβ-induced migration and activation of BV-2 cells as well as the MAPK signaling pathway were detected. Finally, the transcriptional regulation of DOCK by transcription factor 3 (ATF3) was detected by a dual luciferase reporter assay.ResultsDOCK8 expression exerts a significant upregulation in the hippocampus of APP/PS1 mice. However, following the DOCK8 knockdown, there was a significant recovery in the results of the behavioral tests and a notable reduction in microglial expression. Moreover, the high expression of DOCK8 mediated by ATF3 successfully triggered the Cdc42/p38 MAPK signaling pathway, thereby enhancing the migration and recruitment of microglia towards senile plaques, accelerating the production of Aβ plaques.ConclusionsATF3-mediated high expression of DOCK8 accelerates the production of Aβ plaques, and participates in the pathogenesis of AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251336266"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of human induced pluripotent stem cell-derived cortical neurons expressing the six tau isoforms.","authors":"Houbo Jiang, Zichun Xiao, Komal Saleem, Ping Zhong, Li Li, Gaurav Chhetri, Pei Li, Zhongjiao Jiang, Zhen Yan, Jian Feng","doi":"10.1177/13872877251334831","DOIUrl":"https://doi.org/10.1177/13872877251334831","url":null,"abstract":"<p><p>BackgroundThe alternative splicing (AS) of <i>MAPT</i>, which encodes Tau, in the adult human brain produces six major isoforms that play critical roles in the pathogenesis of tauopathies including Alzheimer's disease. Previous efforts have failed to differentiate human induced pluripotent stem cells (hiPSCs) to cortical neurons expressing the six isoforms of Tau.ObjectiveWe aim to develop a differentiation method capable of producing the six Tau isoforms in hiPSC-derived cortical neurons.MethodsWe searched for the optimal concentration, duration and treatment window of morphogens in the differentiation of hiPSCs through embryoid bodies (EBs) to dorsal forebrain neuroepithelial cells then to cortical neurons.ResultsThe combined inhibition of WNT, SHH, and SMAD signaling in EBs generated neuroepithelial cells expressing appropriate dorsal forebrain markers, while suppressing ventral, midbrain, and hindbrain genes. Further differentiation in neurogenic and neurotrophic factors produced MAP2⁺ neurons at day 18. The iPSC-derived neurons expressed markers of all cortical layers and exhibited synapse formation and synaptic physiology. In addition, MAP2⁺ neurons and mitotic cells expressing radial glial markers formed aggregates that could be dissociated to produce mature neurons with similar properties. Most importantly, the six Tau isoforms were expressed from day 80 in a developmentally regulated manner, modeling the situation in human brains on an accelerated timeline.ConclusionsThis chemically defined differentiation method produces a key hallmark of mature human cortical neurons by expressing the six main splicing isoforms of Tau. It will greatly facilitate disease modeling and therapeutic discovery for many human brain disorders involving cortical neurons.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251334831"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aβ_42/40 and p-tau 181 as disease biomarkers in atypical Alzheimer's disease.","authors":"Neha Singh-Reilly, Jonathan Graff-Radford, Danni Li, Michelle M Mielke, Mary M Machulda, Christopher G Schwarz, Matthew L Senjem, Clifford R Jack, Val J Lowe, Keith A Josephs, Jennifer L Whitwell","doi":"10.1177/13872877251333450","DOIUrl":"https://doi.org/10.1177/13872877251333450","url":null,"abstract":"<p><p>BackgroundStudies suggest that plasma Alzheimer's disease (AD) biomarkers may aid in the overall diagnosis of AD, but their utility among patients with atypical clinical presentations of AD are unknown.ObjectiveThe main objective of this study was to determine the relationship between amyloid-β (Aβ) and tau plasma biomarkers and PET measures of both Aβ and tau in atypical AD. The secondary objective was to determine if plasma biomarkers could differentiate patients with different atypical AD phenotypes and whether they were related to measures of disease severity.MethodsWe assessed whether plasma p-tau 181 and Aβ_42/40 were associated with Aβ and tau PET uptake, clinical phenotype and severity in 77 patients with PET biomarker-confirmed atypical AD.ResultsPlasma Aβ_42/40 ratio showed positive associations with tau PET uptake, with higher (more normal) Aβ_42/40 ratio associated with higher tau uptake; the ratio was not associated with Aβ PET. No associations were noted with plasma p-tau 181. Plasma Aβ_42/40 ratio and p-tau 181 concentrations were not associated with AD phenotype or cognitive severity.ConclusionPlasma Aβ_42/40 ratio and p-tau 181 concentrations are not associated with amyloid or tau PET or with clinical severity among individuals presenting with atypical AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333450"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated neuromodulation with low-intensity focused ultrasound in patients with Alzheimer's disease.","authors":"Hyeonseok Jeong, Doyu Kim, Seunghee Na, Byungseok Kim, Jin Kyoung Oh, Eun Kyoung Choi, Sujung Yoon, Marom Bikson, Yong-An Chung, In-Uk Song","doi":"10.1177/13872877251333614","DOIUrl":"https://doi.org/10.1177/13872877251333614","url":null,"abstract":"<p><p>BackgroundLow-intensity focused ultrasound (LIFU), a non-invasive targeted brain stimulation technology, has shown promise for therapeutic applications in Alzheimer's disease (AD) patients. Despite its potential, the implications of repeated LIFU neuromodulation in AD patients remain to be investigated.ObjectiveThis pilot study evaluated the safety and potential to improve cognition and functional connectivity following repeated LIFU treatment in AD patients.MethodsTen early-stage AD patients underwent six sessions of neuronavigation-guided LIFU targeting the left dorsolateral prefrontal cortex (DLPFC) within 2-3 weeks, alongside ongoing standard pharmacotherapy. Neuropsychological assessments and resting-state functional magnetic resonance imaging were performed at baseline and eight weeks post-treatment.ResultsMemory performance (p = 0.02) and functional connectivity between the left DLPFC and both the left perirhinal cortex and left dorsomedial prefrontal cortex (corrected p < 0.05) significantly improved from baseline. Additionally, enhancements in memory performance were positively correlated with increases in functional connectivity of the left DLPFC with the left perirhinal cortex (Kendall's tau = 0.56, p = 0.03). No adverse events were reported during the LIFU treatments or at the subsequent follow-up.ConclusionsLIFU may have the therapeutic potential to enhance both brain network connectivity and memory functions in AD patients. Our results provide a basis for further research, including randomized sham-controlled trials and optimization of stimulation protocols, on LIFU as a supplementary or alternative treatment option for AD.Trial registrationClinical Research Information Service, KCT0008169, Registered on 10 February 2023.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251333614"},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}