Alzheimer's Research & Therapy最新文献

{"title":"Photobiomodulation modulates mitochondrial energy metabolism and ameliorates neurological damage in an APP/PS1 mousmodel of Alzheimer's disease.","authors":"Hongli Chen, Na Li, Na Liu, Hongyu Zhu, Chunyan Ma, Yutong Ye, Xinyu Shi, Guoshuai Luo, Xiaoxi Dong, Tao Tan, Xunbin Wei, Huijuan Yin","doi":"10.1186/s13195-025-01714-w","DOIUrl":"10.1186/s13195-025-01714-w","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease. Amyloid β-protein (Aβ) is one of the key pathological features of AD, which is cytotoxic and can damage neurons, thereby causing cognitive dysfunction. Photobiomodulation (PBM) is a non-invasive physical therapy that induces changes in the intrinsic mechanisms of cells and tissues through low-power light exposure. Although PBM has been employed in the treatment of AD, the effect and precise mechanism of PBM on AD-induced neurological damage are still unclear.</p><p><strong>Methods: </strong>In vivo experiments, PBM (808 nm, 20 mW/cm²) was used to continuously interfere with APP/PS1 mice for 6 weeks, and then their cognitive function and AD pathological changes were evaluated. In vitro experiments, lipopolysaccharide (LPS) was used to induce microglia to model inflammation, and the effect of PBM treatment on microglia polarization status and phagocytic Aβ ability was evaluated. Hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP) was used to study the effect of PBM treatment on mitochondrial energy metabolism in microglia.</p><p><strong>Results: </strong>PBM further ameliorates AD-induced cognitive impairment by alleviating neuroinflammation and neuronal apoptosis, thereby attenuating nerve damage. In addition, PBM can also reduce neuroinflammation by promoting microglial anti-inflammatory phenotypic polarization; Promotes Aβ clearance by enhancing the ability of microglia to engulf Aβ. Among them, PBM regulates microglial polarization and inhibits neuronal apoptosis, which may be related to its regulation of mitochondrial energy metabolism, promotion of oxidative phosphorylation, and inhibition of glycolysis.</p><p><strong>Conclusion: </strong>PBM regulates neuroinflammatory response and inhibits neuronal apoptosis, thereby repairing Aβ-induced neuronal damage and cognitive dysfunction. Mitochondrial energy metabolism plays an important role in PBM in improving nerve injury in AD mice. This study provides theoretical support for the subsequent application of PBM in the treatment of AD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"72"},"PeriodicalIF":7.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787674","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":"Evaluating the diagnostic performance of six plasma biomarkers for Alzheimer's disease and other neurodegenerative dementias in a large Chinese cohort.","authors":"Bin Jiao, Ziyu Ouyang, Yiliang Liu, Cong Zhang, Tianyan Xu, Qijie Yang, Sizhe Zhang, Yuan Zhu, Meidan Wan, Xuewen Xiao, Xixi Liu, Yafang Zhou, Xinxin Liao, Weiwei Zhang, Shilin Luo, Beisha Tang, Lu Shen","doi":"10.1186/s13195-025-01712-y","DOIUrl":"10.1186/s13195-025-01712-y","url":null,"abstract":"<p><strong>Background: </strong>Ethnic variations and detection methods may lead to differences in diagnostic biomarkers of dementia, and few comparative studies have evaluated the six plasma biomarkers of Alzheimer's disease (AD) and other neurodegenerative dementias in the Chinese population.</p><p><strong>Methods: </strong>A cross-sectional cohort of 668 participants were enrolled, including 245 amnesic mild cognitive impairment (aMCI) or AD patients with Aβ positive pathology, 67 with frontotemporal dementia (FTD), 100 with progressive supranuclear palsy (PSP), 72 with dementia with Lewy bodies (DLB) and 184 healthy controls. Additionally, a longitudinal subset of 19 aMCI and 30 AD patients was followed for an average period of 1 year. Plasma biomarkers, including p-tau181, p-tau217, p-tau231, NfL, GFAP, and α-synuclein, were simultaneously measured using a novel single molecular array method. Aβ42 and p-tau181 levels in CSF, amyloid PET and structural MRI were measured.</p><p><strong>Results: </strong>Plasma p-tau217 and p-tau231 were most effective in diagnosing aMCI/AD (AUC = 0.95 and 0.93, respectively), while p-tau217, p-tau231 and p-tau181 presented the best differential diagnosis for AD from PSP, FTD and DLB respectively (AUC = 0.84, 0.81 and 0.83). α-synuclein was presented as the best biomarker for PSP variant and behavior variant FTD subtypes (AUC = 0.81 and 0.74, respectively). Among them, p-tau217, p-tau231, GFAP and a-synuclein were negatively correlated with CSF Aβ42/40, while p-tau217 and GFAP were positively correlated with CSF p-tau181. Besides, p-tau181, p-tau217, and GFAP were associated with temporal lobe volume, while p-tau231 and GFAP were associated with frontal lobe volume. Longitudinal analysis showed the higher p-tau181 could predict the cognitive decline progression.</p><p><strong>Conclusions: </strong>This study validate the practicality of blood biomarkers in the Chinese Han population using a novel single molecule immune detection method. Through the clinical performance study for several biomarkers, we found the plasma p-tau217 was the most effective biomarker in AD diagnosis, and p-tau showed high accuracy for differential diagnosis of AD from other dementia, GFAP is associated with multiple aspects of AD pathology, and frontal and temporal lobe volume, and p-tau181 can reflect the dynamic cognitive decline of AD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"71"},"PeriodicalIF":7.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778832","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":"Integrative network analysis reveals novel moderators of Aβ-Tau interaction in Alzheimer's disease.","authors":"Akihiro Kitani, Yusuke Matsui","doi":"10.1186/s13195-025-01705-x","DOIUrl":"10.1186/s13195-025-01705-x","url":null,"abstract":"<p><strong>Background: </strong>Although interactions between amyloid-beta and tau proteins have been implicated in Alzheimer's disease (AD), the precise mechanisms by which these interactions contribute to disease progression are not yet fully understood. Moreover, despite the growing application of deep learning in various biomedical fields, its application in integrating networks to analyze disease mechanisms in AD research remains limited. In this study, we employed BIONIC, a deep learning-based network integration method, to integrate proteomics and protein-protein interaction data, with an aim to uncover factors that moderate the effects of the Aβ-tau interaction on mild cognitive impairment (MCI) and early-stage AD.</p><p><strong>Methods: </strong>Proteomic data from the ROSMAP cohort were integrated with protein-protein interaction (PPI) data using a Deep Learning-based model. Linear regression analysis was applied to histopathological and gene expression data, and mutual information was used to detect moderating factors. Statistical significance was determined using the Benjamini-Hochberg correction (p < 0.05).</p><p><strong>Results: </strong>Our results suggested that astrocytes and GPNMB + microglia moderate the Aβ-tau interaction. Based on linear regression with histopathological and gene expression data, GFAP and IBA1 levels and GPNMB gene expression positively contributed to the interaction of tau with Aβ in non-dementia cases, replicating the results of the network analysis.</p><p><strong>Conclusions: </strong>These findings suggest that GPNMB + microglia moderate the Aβ-tau interaction in early AD and therefore are a novel therapeutic target. To facilitate further research, we have made the integrated network available as a visualization tool for the scientific community (URL: https://igcore.cloud/GerOmics/AlzPPMap ).</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"70"},"PeriodicalIF":7.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771072","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":"Effects of 52 weeks of precuneus rTMS in Alzheimer's disease patients: a randomized trial.","authors":"Giacomo Koch, Elias Paolo Casula, Sonia Bonnì, Ilaria Borghi, Martina Assogna, Francesco Di Lorenzo, Romina Esposito, Michele Maiella, Alessia D'Acunto, Matteo Ferraresi, Lucia Mencarelli, Valentina Pezzopane, Caterina Motta, Emiliano Santarnecchi, Marco Bozzali, Alessandro Martorana","doi":"10.1186/s13195-025-01709-7","DOIUrl":"10.1186/s13195-025-01709-7","url":null,"abstract":"<p><strong>Background: </strong>Personalized repetitive transcranial magnetic stimulation (rTMS) of the precuneus (PC) is emerging as a new non-invasive therapeutic approach in treating Alzheimer's disease (AD). Here we sought to investigate the effects of 52 weeks of rTMS applied over the PC on cognitive functions in patients with mild-to-moderate dementia due to AD.</p><p><strong>Methods: </strong>Forty-eight patients with mild-to-moderate dementia due to AD were enrolled for the study. Of those 31 patients were extended to 52 weeks after being included in a 24-week trial (NCT03778151) with the same experimental design. The trial included a 52-week treatment with a 2-week intensive course where rTMS (or sham) was applied over the PC daily (5 times per week, Monday to Friday), followed by a 50-week maintenance phase in which the same stimulation was applied once weekly. Personalization of rTMS treatment was established using neuronavigated TMS in combination with electroencephalography (TMS-EEG). The primary outcome measure was change from baseline to week 52 of the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Secondary outcomes included score changes in the Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)₁₁, Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) and Neuropsychiatric Inventory (NPI). Changes in cortical activity and connectivity were monitored by TMS-EEG.</p><p><strong>Results: </strong>Among 48 patients randomized (mean age 72.8 years; 56% women), 32 (68%) completed the study. Repetitive TMS of the PC (PC-rTMS) had a significant effect on the primary outcome measure. The estimated mean change in CDR-SB after 52 week was 1.36 for PC-rTMS (95% confidence interval (CI) [0.68, 2.04]) and 2.45 for sham-rTMS group (95%CI [1.85, 3.05]). There were also significant effects for the secondary outcomes ADAS-Cog₁₁, ADCS-ADL and NPI scores. Stronger DMN connectivity at baseline was associated with favorable response to rTMS treatment.</p><p><strong>Conclusions: </strong>Fifty-two weeks of PC-rTMS may slow down the impairment of cognitive functions, activities of daily living and behavioral disturbances in patients with mild-to-moderate AD. Further multicenter studies are needed to confirm the clinical potential of DMN personalized rTMS.</p><p><strong>Trial registration: </strong>The study was registered on the clinicaltrial.gov website on 07-07-2022 (NCT05454540).</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"69"},"PeriodicalIF":7.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771064","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 plasma p-tau217 in a memory clinic cohort using the Lumipulse automated platform.","authors":"Francisco Martínez-Dubarbie, Armando Guerra-Ruiz, Sara López-García, Carmen Lage, Marta Fernández-Matarrubia, Álvaro Nevado-Cáceres, María Rivera-Sánchez, Andrea Valera-Barrero, Ana Pozueta-Cantudo, María García-Martínez, Andrea Corrales-Pardo, María Bravo, Marcos López-Hoyos, Juan Irure-Ventura, Enrique Marco de Lucas, Marta Drake-Pérez, Nancy Heidy Cahuana-Santamaría, María Teresa García-Unzueta, Pascual Sánchez-Juan, Eloy Rodríguez-Rodríguez","doi":"10.1186/s13195-025-01719-5","DOIUrl":"10.1186/s13195-025-01719-5","url":null,"abstract":"<p><strong>Background: </strong>Plasma biomarkers for Alzheimer's disease (AD) are a promising tool for accessible and accurate biological diagnostics. However, data in clinical practice are needed to better understand their diagnostic and prognostic ability in memory unit patients.</p><p><strong>Methods: </strong>We analyzed plasma phosphorylated tau at threonine 217 (p-tau217) and neuroflament light chain (NfL) levels and AD cerebrospinal fluid (CSF) biomarkers in a group of 493 subjects using the Lumipulse G600II platform. The sample includes 340 patients from our memory unit (142 dementia, 186 mild cognitive impairment, and 12 with subjective complaints) and 153 cognitively unimpaired volunteers. We have correlated plasma and CSF biomarkers; we have analyzed plasma biomarker levels as a function of clinical diagnosis, cognitive status and amyloid status. We have also studied the ability of p-tau217 to discriminate between amyloid-positive and -negative subjects according to CSF using receiver operating characteristic curves.</p><p><strong>Results: </strong>Plasma p-tau217 correlated significantly with CSF Aβ42/Aβ40 (Rho = -0.75; p-value < 0.001), p-tau181 (r = 0.66; p-value < 0.001), and t-tau (r = 0.59; p-value < 0.001). Plasma NfL correlated with CSF NfL (r = 0.48; p-value < 0.001). By clinical diagnosis, plasma p-tau217 levels showed to be higher in AD patients than in healthy controls (difference = 0.63 pg/ml; p-value < 0.001), FTD (difference = 0.60 pg/ml; p-value < 0.001), and nondegenerative dementias (difference = 0.61 pg/ml; p-value < 0.001). Plasma p-tau217 showed an area under the curve of 0.95 to discriminate between A + and A- subjects (95%CI 0.93-0.97).</p><p><strong>Conclusion: </strong>Plasma p-tau217 shows excellent results for detecting amyloid pathology at brain level in a clinical setting with an AUC of 0.95. It is a highly specific marker of AD and increases progressively along the disease continuum. Using plasma p-tau217 as an initial diagnostic tool with cut-offs at sensitivities and specificities of 95 or 97.5% could save between 57.4-84.8% of LP/PETs with diagnostic accuracies of 95-97%. Plasma NfL increases progressively at different cognitive stages.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"68"},"PeriodicalIF":7.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717624","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":"Accelerometer-derived \"weekend warrior\" physical activity, sedentary behavior, and risk of dementia.","authors":"Yuye Ning, Meilin Chen, Hao Yang, Jianping Jia","doi":"10.1186/s13195-024-01657-8","DOIUrl":"10.1186/s13195-024-01657-8","url":null,"abstract":"<p><strong>Background: </strong>Research has shown that sedentary behavior (SB) may increase dementia risk, but it remains unclear whether concentrated moderate to vigorous physical activity (MVPA) can compensate such negative effects. This study aimed to explore the association between different MVPA patterns combined with SB time and the risk of dementia.</p><p><strong>Methods: </strong>This prospective study used data from the UK Biobank cohort, which provided accelerometer-based physical activity data for a full week from February 2013 to December 2015. Participants were categorized into \"weekend warriors (WW)\" group, engaged in more than 50% MVPA (≥ 150 min/week) on 1 to 2 days; inactive group (total MVPA < 150 min/week); and regular group, who met the recommended MVPA (≥ 150 min/week) but not WW. The participants were further divided into six groups based on SB duration (≥ 8.52 h/day or < 8.52 h/day). A multivariable Cox model was used to assess the relationship between these patterns and the risk of dementia, adjusted by age, gender, ethnicity, Townsend deprivation index, education level, employment status, alcohol consumption, smoking, BMI, and baseline comorbidities (including cardiovascular disease, hypertension, and diabetes).</p><p><strong>Results: </strong>We included 91,948 participants without dementia at baseline. During a median follow-up of 7.93 years, 736 participants developed all-cause dementia. When the MVPA threshold was set at 150 min per week, 16,149 participants (17.5%) were classified as WW with long SB, 19,055 (20.7%) as regular with long SB, and 21,909 (23.8%) as inactive with long SB. Compared to inactive and long SB time, the WW group showed a reduction in dementia risk (WW with long SB time: HR = 0.69, 95% CI: 0.54-0.87, P = 0.002; WW with short SB time: HR = 0.74, 95% CI: 0.56-0.97, P = 0.029). And regular group with shorter SB time was associated with a lower dementia risk (HR = 0.75, 95% CI: 0.59-0.96, P = 0.021), but not in the group with longer SB time.</p><p><strong>Conclusions: </strong>The WW pattern may help mitigate the dementia risk associated with prolonged SB, suggesting that the quality and intensity of physical activity are also important factors.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"67"},"PeriodicalIF":7.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690679","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":"Impact of effective connectivity within the Papez circuit on episodic memory: moderation by perivascular space function.","authors":"Ling-Ling Li, Jie Ma, Jia-Jia Wu, Xin Xue, Mou-Xiong Zheng, Xu-Yun Hua, Qi-Hao Guo, Jian-Guang Xu","doi":"10.1186/s13195-025-01717-7","DOIUrl":"10.1186/s13195-025-01717-7","url":null,"abstract":"<p><strong>Background and objectives: </strong>The formation and retrieval of episodic memory is dependent on the coordinated activity of multiple brain regions and neural networks, with the Papez circuit playing a critical role in this process. Recently, the role of the perivascular space (PVS) in cognitive function has garnered increasing attention. However, the role of PVS function between neural circuits and cognitive function in amnestic mild cognitive impairment (aMCI) patients remains unknown. Therefore, this study aims to (1) investigate alterations in the effective connectivity of the Papez circuit and PVS function in patients with aMCI and (2) explore the role of PVS function between the effective connectivity of the Papez circuit and episodic memory.</p><p><strong>Methods: </strong>Sixty participants, all of whom underwent multimodal MRI (fMRI, dMRI, and sMRI) and neuropsychological testing, were recruited for this case‒control study. General linear models were used to compare the effective connectivity within the Papez circuit and PVS function between aMCI patients and healthy controls (HCs) and further explore the role of PVS function between the effective connectivity within the Papez circuit and episodic memory.</p><p><strong>Results: </strong>The effective connectivity between multiple critical regions within the Papez circuit, notably in the hippocampus, anterior cingulate cortex, and parahippocampal gyrus, was significantly weakened in aMCI patients. Moreover, a significant reduction in the along the perivascular space (ALPS) index was observed among aMCI patients, accompanied by a marked increase in PVS volume, indicating significant PVS dysfunction. Further moderation analysis revealed that PVS function moderated the relationship between effective connectivity within the Papez circuit and episodic memory.</p><p><strong>Conclusions: </strong>The effective connectivity within the Papez circuit and PVS function are closely related to cognitive function, particularly episodic memory, and enhancing PVS function may serve as a novel therapeutic target for slowing cognitive decline.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"66"},"PeriodicalIF":7.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668848","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":"Tau-PET pathology in the subregions of the amygdala and its associations with cognitive performance and neuropsychiatric symptoms in autosomal dominant Alzheimer's disease.","authors":"Catarina Tristão-Pereira, Stephanie Langella, Justin S Sanchez, Vincent Malotaux, Bing He, Jorge Alcina, Jairo E Martinez, Zoe Rubinstein, Ana Baena, Clara Vila-Castelar, Averi Giudicessi, Liliana Ramirez Gomez, Claudia Ramos, Daniel Vasquez, David Aguillon, Heidi I L Jacobs, Reisa A Sperling, Keith Johnson, Jennifer R Gatchel, Yakeel T Quiroz","doi":"10.1186/s13195-025-01711-z","DOIUrl":"10.1186/s13195-025-01711-z","url":null,"abstract":"<p><strong>Background: </strong>The amygdala plays a role in behavior and emotional response and is vulnerable to Alzheimer's disease (AD) pathology, yet little is known about amygdala tau accumulation before clinical symptom onset. To investigate whether certain amygdala nuclei are particularly vulnerable to degeneration and might underlie early neuropsychiatric symptoms in AD, we aimed to characterize subregional amygdala tau pathology and its correlates associations with established biomarkers of early AD and cognitive-behavioral measures in Presenilin-1 E280A mutation carriers of autosomal dominant AD.</p><p><strong>Methods: </strong>Participants included 25 cognitively unimpaired mutation carriers and 37 non-carrier family members from the Colombia-Boston (COLBOS) Biomarker Study. Measures included 18F-flortaucipir, 11C-Pittsburgh compound B, Consortium to Establish a Registry for Alzheimer's Disease Word List Learning, Trail Making Test, Geriatric Depression Scale, and Geriatric Anxiety Inventory. We examined group differences in amygdala tau levels (whole amygdala, lateral nucleus and basal nucleus) and analyzed tau associations with disease markers and clinical measures.</p><p><strong>Results: </strong>Amygdala tau levels were higher in unimpaired carriers compared to non-carriers. Among carriers, the basal nucleus showed a greater tau burden than the lateral nucleus, and tau accumulation correlated with closer estimated age to clinical onset and increased cortical amyloid. Additionally, tau in both the basal and lateral amygdala was associated with poorer working memory, lower executive function and greater depressive symptoms. However, amygdala tau did not correlate with symptoms of anxiety. Notably, tau levels in the basal amygdala differentiated carriers from non-carriers, with higher predictive accuracy when neuropsychiatric measures were included.</p><p><strong>Conclusions: </strong>These findings suggest that in autosomal dominant AD, tau accumulation in the amygdala begins early in the basal nucleus, while both the basal and the lateral nuclei are associated with early cognitive deficits and depressive symptoms. The nuclei's differential vulnerability to pathology underscores the importance of investigating tau spread within amygdala-associated networks, relative to the early clinical manifestations of AD. This study reinforces the potential of amygdala tau burden as a valuable biomarker for preclinical AD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"64"},"PeriodicalIF":7.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661956","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":"Impact of sleep apnea on alzheimer's disease in relation to sex: an 8-year longitudinal follow-up study of a nationwide cohort.","authors":"Su Jin Chung, Sung Hoon Kang, Minwoong Kang, Yunjin Choi, Yu Jeong Park, Hayom Kim, Kyungmi Oh, Seong-Beom Koh, Jung Bin Kim","doi":"10.1186/s13195-024-01667-6","DOIUrl":"10.1186/s13195-024-01667-6","url":null,"abstract":"<p><strong>Background: </strong>We aimed to investigate the association between sleep apnea and incident dementia (dementia of the Alzheimer type [DAT] and vascular dementia) and whether differences in the effects of sleep apnea on dementia depend on sex. Furthermore, we sought to determine whether obesity affects the sex-specific relationship between sleep apnea and dementia.</p><p><strong>Methods: </strong>We used de-identified data on patients with sleep apnea and a control group aged ≥ 50 years from the Korean National Health Insurance Service. After propensity score matching to balance age and sex between the patient and control groups, 30,111 individuals with sleep apnea (patient group) and 121,528 individuals without sleep apnea (control group) were included. To investigate the impact of sleep apnea on the development of dementia, we used Cox proportional hazards regression after controlling for potential confounders.</p><p><strong>Results: </strong>Sleep apnea was predictive of developing DAT in both women (hazard ratio [HR] = 1.30, 95% confidence interval [CI] 1.16-1.44, p < 0.001) and men (HR = 1.13, 95% CI 1.03-1.24, p = 0.012). The adverse effects of sleep apnea on DAT were more prominent in women than in men (p = 0.015 for sleep apnea×sex). Furthermore, obesity affected the sex-specific relationship between sleep apnea and DAT. Specifically, the adverse effects of obese sleep apnea on the DAT were more pronounced in women than in men (p = 0.002 for obese sleep apnea×sex). In contrast, there were no differences in the effects of non-obese sleep apnea on DAT between women and men (p = 0.667 for non-obese sleep apnea×sex).</p><p><strong>Conclusions: </strong>Our results highlight sex differences in the adverse effects of sleep apnea on DAT. Furthermore, these results suggest that sex-specific strategies for controlling sleep apnea are necessary to prevent DAT.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"65"},"PeriodicalIF":7.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668850","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: Cornuside alleviates cognitive impairments induced by Aβ_1-42 through attenuating NLRP3-mediated neurotoxicity by promoting mitophagy.","authors":"Fulin Zhou, Wenwen Lian, Xiaotang Yuan, Zexing Wang, Congyuan Xia, Yu Yan, Wenping Wang, Zhuohang Tong, Yungchi Cheng, Jiekun Xu, Jun He, Weiku Zhang","doi":"10.1186/s13195-025-01715-9","DOIUrl":"10.1186/s13195-025-01715-9","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"17 1","pages":"63"},"PeriodicalIF":7.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661953","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}