Journal of Alzheimer's Disease最新文献

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Investigating the effects of 40 Hz sound stimulation on Alzheimer's disease pathways: Modulation of amyloid-β42 secretion, tau phosphorylation, phagocytosis, and autophagy. 研究40hz声刺激对阿尔茨海默病通路的影响:淀粉样蛋白-β42分泌、tau磷酸化、吞噬和自噬的调节。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-04 DOI: 10.1177/13872877251339774
Yuan-Han Yang, Hsi-Wen Chang, Ching-Fang Chien, Tzyh-Chyuan Hour
{"title":"Investigating the effects of 40 Hz sound stimulation on Alzheimer's disease pathways: Modulation of amyloid-β42 secretion, tau phosphorylation, phagocytosis, and autophagy.","authors":"Yuan-Han Yang, Hsi-Wen Chang, Ching-Fang Chien, Tzyh-Chyuan Hour","doi":"10.1177/13872877251339774","DOIUrl":"10.1177/13872877251339774","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is the main cause of dementia in an aging society. Previous studies have demonstrated that non-invasive light flicker and sound with gamma frequency oscillations can modulate AD-related pathology in AD mice, potentially improving patient outcomes. However, the molecular mechanism by which sound with gamma frequency oscillations inhibits the expression of amyloid-β<sub>1-42</sub> (Aβ<sub>42</sub>) and the phosphorylation of tau, and modulating cell autophagy in nerve cells are still unclear.ObjectiveThis study aimed to explore the molecular effects of 40 Hz sound stimulation on AD-related pathways in a cellular model.MethodsWe designed a 40 Hz stimulating sound (H<sup>+</sup> multi-frequency audio) for this study, and cells were exposed to H<sup>+</sup> multi-frequency audio. The concentration of Aβ<sub>42</sub> was quantified by enzyme-linked immunosorbent assay. Protein levels were examined by western blotting. Phagocytosis was examined by confocal microscopy and phagocytic analysis.ResultsFirst, we found that exposure to the 40 Hz stimulating sound inhibited the secretion of Aβ<sub>42</sub> by activating the AβPP/ADAM10 pathway and suppressing the AβPP/BACE1 pathway. Second, 40 Hz stimulating sound inhibited tau phosphorylation at Thr181 through the inactivation of the Akt/mTOR pathway. Third, 40 Hz stimulating sound enhanced the phagocytosis and autophagy of Aβ<sub>42</sub> through the AMPK/ULK/LC3B pathway in cells.ConclusionsOur study showed that 40 Hz stimulating sound is involved in the inhibition of Aβ<sub>42</sub> secretion, p-Tau protein expression, and the promotion of phagocytosis and Aβ<sub>42</sub> autophagy in cells. We suggest that 40 Hz stimulating sound could be a potential intervention to attenuate AD progression in the future.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"184-196"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966724","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}
引用次数: 0
Ethnic disparities in care needs among individuals with cognitive impairment. 认知障碍患者护理需求的种族差异。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-04-21 DOI: 10.1177/13872877251334819
Roshanak Mehdipanah, Emily M Briceño, Madelyn Malvitz, Wen Chang, Steven G Heeringa, Darin B Zahuranec, Deborah A Levine, Kenneth M Langa, Xavier F Gonzales, Nelda Garcia, Noreen Khan, Lewis B Morgenstern
{"title":"Ethnic disparities in care needs among individuals with cognitive impairment.","authors":"Roshanak Mehdipanah, Emily M Briceño, Madelyn Malvitz, Wen Chang, Steven G Heeringa, Darin B Zahuranec, Deborah A Levine, Kenneth M Langa, Xavier F Gonzales, Nelda Garcia, Noreen Khan, Lewis B Morgenstern","doi":"10.1177/13872877251334819","DOIUrl":"10.1177/13872877251334819","url":null,"abstract":"<p><p>BackgroundAs more individuals with cognitive impairment and dementia (CID) remain at home, greater needs arise, necessitating additional support.ObjectiveTo examine ethnic differences in the needs of individuals with CID among Mexican American (MA) and non-Hispanic White (NHW) participants.MethodsAdults 65 + with possible cognitive impairment (Montreal Cognitive Assessment score < 26), and their caregivers living in Nueces County, Texas, were included. We used the Camberwell Assessment of Need for the Elderly (CANE) tool to study the needs (accommodations, self-care, continence, physical health, emotional well-being, social relationships, and availability of support networks) and their domains of individuals with CID including environmental, physical, psychological and social needs. Using negative binomial and Poisson regressions, ethnic differences were examined within each domain.ResultsA total of 473 participants were included. NHW participants (N = 150) were slightly older (75.5 versus 72.7 years) and had higher rates of MCI and dementia (55% versus 47%) compared to MA participants (N = 323). All participants reported high levels of needs (met or unmet). Furthermore, although NHW participants reported having fewer social needs (met or unmet) compared to MA participants (Incident Rate Ratio [IRR]=-0.79; 97.5%CI:0.63-0.98), NHW participants had a greater level of unmet needs when it came to social needs compared to MA participants (IRR = 1.85; 97.5%CI:1.33-2.57).ConclusionsFindings indicate high levels of needs among individuals with CID. There also exist ethnic differences, with NHW participants having greater unmet needs in social areas. Enhancing access to resources and support systems is essential for equitable support for individuals with CID across various ethnic backgrounds.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"69-77"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990885","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}
引用次数: 0
Correlations between agitation and other neuropsychiatric symptoms in each stage of Alzheimer's disease: A re-analysis of CATIE-AD. 躁动与阿尔茨海默病各阶段其他神经精神症状的相关性:CATIE-AD的再分析
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-05 DOI: 10.1177/13872877251340402
Tomoyuki Nagata, Shinichiro Nakajima, Shinsuke Kito, Shunichiro Shinagawa
{"title":"Correlations between agitation and other neuropsychiatric symptoms in each stage of Alzheimer's disease: A re-analysis of CATIE-AD.","authors":"Tomoyuki Nagata, Shinichiro Nakajima, Shinsuke Kito, Shunichiro Shinagawa","doi":"10.1177/13872877251340402","DOIUrl":"10.1177/13872877251340402","url":null,"abstract":"<p><p>BackgroundAmong neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), agitation has been shown to occur commonly in the course of AD, overlapping or comorbid with other NPSs.ObjectiveThe proportion of patients with agitation and the severity of agitation appear to differ depending on the neurocognitive stage of AD, and knowledge about the characteristic comorbid symptom pattern may help in elucidation of the underlying mechanism.MethodsAmong 421 clinic-based patients with AD, we re-analyzed the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) to examine the correlations between the scores for agitation and those for other Neuropsychiatric Inventory subscales in each neurocognitive stage of AD (mild, moderate, and severe) classified according to scores in Mini-Mental State Examination.ResultsThe scores for agitation were positively and robustly correlated with the scores for irritability in all stages of AD, and with the scores for anxiety in the moderate and severe stages. The scores for agitation were also correlated with those for sleep disorders in severe AD stage or disinhibition in the moderate AD stage. Multiple regression analysis identified irritability influencing the agitation in moderate and severe stages, and sleep disorders influencing the agitation in the severe stage.ConclusionsAs comorbid NPSs with agitation, characteristic affective, impulsive, and circadian abnormalities may be relevant to generate diverse subsyndromes in AD. Irritability consistently causes agitated behaviors, including refusal to take one's own care, and diurnal rhythm disorder in the severe AD stage may also cause poor acceptance for self-care.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"342-351"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019747","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}
引用次数: 0
Disruptive resting state networks characterizing depressive comorbidity in Alzheimer's disease and mild cognitive impairment. 阿尔茨海默病和轻度认知障碍中抑郁症共病的破坏性静息状态网络特征。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-06 DOI: 10.1177/13872877251337770
Alessandro von Gal, Dario Papa, Marco D'Auria, Laura Piccardi
{"title":"Disruptive resting state networks characterizing depressive comorbidity in Alzheimer's disease and mild cognitive impairment.","authors":"Alessandro von Gal, Dario Papa, Marco D'Auria, Laura Piccardi","doi":"10.1177/13872877251337770","DOIUrl":"10.1177/13872877251337770","url":null,"abstract":"<p><p>BackgroundDepressive comorbidity in neurodegeneration has been shown to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, its pathophysiology is not completely understood.ObjectiveHere, we characterize aberrant functional resting state networks (RSNs) characterizing depressive comorbidity in both AD and MCI.MethodsWe conducted a systematic literature review on Scopus, PubMed, and Web of Science to extract experiments that compared resting state scans of depressed and non-depressed MCI or AD patients. We employed Activation Likelihood Estimation (ALE) meta-analysis on eligible studies resulting from the search, to describe regions of significant co-activation across studies.ResultsThe systematic search resulted in 17 experiments, with 303 participants in total. The ALE yielded 10 clusters of significant co-activation distributed in the five major RSNs and across cortico-basal ganglia-thalamic circuits.ConclusionsDepressive comorbidity in neurodegeneration presents signature aberrant resting-state fluctuations. Understanding these within- and between-network alterations may be useful for future diagnostic and therapeutic applications.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"18-37"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004744","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}
引用次数: 0
Loss of WDR23 slows the rate of age-related cognitive decline with elevated amyloid burden. WDR23的缺失减缓了淀粉样蛋白负担升高的年龄相关认知能力下降的速度。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-04 DOI: 10.1177/13872877251339776
Jiahui Liu, Chatrawee Duangjan, Nguyen M Phan, Sean P Curran
{"title":"Loss of WDR23 slows the rate of age-related cognitive decline with elevated amyloid burden.","authors":"Jiahui Liu, Chatrawee Duangjan, Nguyen M Phan, Sean P Curran","doi":"10.1177/13872877251339776","DOIUrl":"10.1177/13872877251339776","url":null,"abstract":"<p><p>BackgroundWDR23 is a regulator of cellular proteostasis and oxidative stress response processes that are critically involved in the pathogenesis of Alzheimer's disease (AD). Dysregulation of these pathways can contribute to amyloid-β (Aβ) and tau pathologies, ultimately leading to cognitive impairment.ObjectiveWe explored the effects of <i>Wdr23</i> knockout on key AD-related pathologies, including transcriptomic changes, Aβ and tau pathology, and cognitive function in the 3xTg-AD mouse model of early onset familial AD.MethodsTranscriptomic analysis of hippocampal tissue was performed to identify <i>Wdr23</i>-dependent gene expression changes across age groups. Aβ and tau pathology was assessed via immunohistochemistry. Behavioral assays were conducted to determine cognitive function and locomotor activity.ResultsTranscriptomic data revealed an age-dependent effect of <i>Wdr23</i> knockout on gene expression, with enrichment of pathways related to cognition and synaptic plasticity, especially middle-age and aged mice. Interestingly, while <i>Wdr23</i> knockout exacerbated amyloid plaque accumulation in older mice, it did not impact tau pathology. Behaviorally, <i>Wdr23</i> knockout mice exhibited improved cognitive function and enhanced activity levels compared to wild-type counterparts, suggesting a dissociation between Aβ pathology and cognitive performance. Additionally, we observed age-related changes in NRF2 target gene activation but declined in <i>Wdr23</i> knockout mice over time.ConclusionsOur findings highlight a complex relationship between proteostasis, amyloid pathology, and cognitive outcomes in AD, warranting further investigation into the specific mechanisms by which <i>Wdr23</i> modulates these processes. This study suggests that targeting proteostasis pathways could offer potential therapeutic benefits, particularly in preserving cognitive function, even in the presence of amyloid pathology.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"218-229"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005720","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}
引用次数: 0
Acute cerebral blood flow response to heavy cream ingestion in older adults: A non-randomized pilot study. 老年人摄入浓奶油后的急性脑血流反应:一项非随机先导研究。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-19 DOI: 10.1177/13872877251340369
Nathaniel K Ashford, Swati Rane, Kristen M Farris, Jasroop Miglani, Baocheng Chu, Daniel S Hippe, Tarun Gandhi, Angela J Hanson
{"title":"Acute cerebral blood flow response to heavy cream ingestion in older adults: A non-randomized pilot study.","authors":"Nathaniel K Ashford, Swati Rane, Kristen M Farris, Jasroop Miglani, Baocheng Chu, Daniel S Hippe, Tarun Gandhi, Angela J Hanson","doi":"10.1177/13872877251340369","DOIUrl":"10.1177/13872877251340369","url":null,"abstract":"<p><p>BackgroundHypertension and the <i>APOE4</i> allele are known risk factors for Alzheimer's disease (AD) and E4 carriers show different blood pressure (BP) and cognitive responses to high fat feeding.ObjectiveWe investigated the influence of these factors on global cerebral blood flow (CBF) and four regions of interest (ROIs) (angular gyrus, hippocampus, posterior cingulate, temporal lobe) using arterial spin labeling (ASL) MRI in fasting state and after ingestion of heavy cream in older adults.Methods29 adults (age in years 66.8 ± 4.1) underwent baseline and 1, 2, 3-h ASL MRI after ingestion of 100 mL heavy cream. We used pCASL MRI with background suppression to measure CBF in ml/100 g/min. Statistical analyses included mixed-effects modeling and Pearson correlation to ascertain whether CBF changed over time and how variables influenced results.ResultsGlobal CBF decreased at 1-, 2-, and 3-h post-heavy cream, compared to time 0 (overall change 7.11%, p < 0.01); recapitulated in 3 of 4 ROIs. Mean arterial pressure emerged as a predictive variable for both baseline and post-heavy cream CBF (β = -0.25, 95% CI = -0.39, -0.10, p = 0.002). Individuals with higher BP demonstrated reduced CBF, particularly in posterior cingulate and temporal lobe (β = -5.50, 95% CI = -9.9, -1.09; β = -6.28, 95% CI = -12.35, -0.21, respectively, both p < 0.05). Examination of correlations with BP and change scores revealed that this relationship was driven largely by E4 carriers.ConclusionsCBF decreased after ingestion of heavy cream, globally and in regions known to be important in AD, and this finding was driven by E4 carriers with higher BP.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"331-341"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101762","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}
引用次数: 0
Association of rare APOE missense variants with Alzheimer's disease in the Japanese population. 日本人群中罕见APOE错义变异与阿尔茨海默病的关系
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1177/13872877251340710
Akinori Miyashita, Ai Obinata, Norikazu Hara, Risa Mitsumori, Daita Kaneda, Yoshio Hashizume, Terunori Sano, Masaki Takao, Ramil Gabdulkhaev, Mari Tada, Akiyoshi Kakita, Akira Arakawa, Maho Morishima, Shigeo Murayama, Yuko Saito, Hiroyuki Hatsuta, Tomoyasu Matsubara, Akio Akagi, Yuichi Riku, Hiroaki Miyahara, Jun Sone, Mari Yoshida, Haruyasu Yamaguchi, Tamao Tsukie, Mai Hasegawa, Kensaku Kasuga, Masataka Kikuchi, Hiroyasu Akatsu, Ryozo Kuwano, Takeshi Iwatsubo, Shumpei Niida, Kouichi Ozaki, Takeshi Ikeuchi
{"title":"Association of rare <i>APOE</i> missense variants with Alzheimer's disease in the Japanese population.","authors":"Akinori Miyashita, Ai Obinata, Norikazu Hara, Risa Mitsumori, Daita Kaneda, Yoshio Hashizume, Terunori Sano, Masaki Takao, Ramil Gabdulkhaev, Mari Tada, Akiyoshi Kakita, Akira Arakawa, Maho Morishima, Shigeo Murayama, Yuko Saito, Hiroyuki Hatsuta, Tomoyasu Matsubara, Akio Akagi, Yuichi Riku, Hiroaki Miyahara, Jun Sone, Mari Yoshida, Haruyasu Yamaguchi, Tamao Tsukie, Mai Hasegawa, Kensaku Kasuga, Masataka Kikuchi, Hiroyasu Akatsu, Ryozo Kuwano, Takeshi Iwatsubo, Shumpei Niida, Kouichi Ozaki, Takeshi Ikeuchi","doi":"10.1177/13872877251340710","DOIUrl":"10.1177/13872877251340710","url":null,"abstract":"<p><p>BackgroundLittle is known about the rare missense variants (RMVs) of <i>APOE</i> in East Asians, including the Japanese, and their association with Alzheimer's disease (AD) and lipid metabolism.ObjectiveTo identify <i>APOE</i> RMVs in the Japanese population and investigate their association with AD and lipid metabolism, including low-density lipoprotein cholesterol levels.Methods<i>APOE</i> RMVs were explored in the Niigata (NIG; 2589 subjects) and Tohoku (ToMMo; 3307 subjects) cohorts. A case-control study included 6261 AD cases and 16,331 controls, all of whom were aged 65 or older. Sanger sequencing, whole-exome sequencing, or a combination of both was performed on the NIG subjects. We used the genotype data from the ToMMo cohort. <i>APOE</i> RMV frequencies in the Japanese population were compared with various ethnic populations. Associations between <i>APOE</i> RMV genotypes, AD, and lipoproteins were examined.ResultsFourteen RMVs were identified (minor allele frequency 0.02-0.73%), with 10 unique to East Asians. Five previously reported RMVs, such as the Christchurch RMV, were absent in Japanese individuals. Two RMVs (rs140808909 and rs190853081), which exhibit complete linkage disequilibrium, were found to have protective effects against AD: <i>p</i><sub>Bonferroni</sub> = 4.28E-02, OR (95% CI) = 0.70 (0.54-0.92). No significant differences in cholesterol levels were observed between RMV carriers and non-carriers.ConclusionsThe two <i>APOE</i> RMVs identified in Japanese individuals may have exhibited potential protective effects against AD. Further large-scale studies are needed to confirm these findings and to explore their roles in AD and lipid metabolism.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"363-377"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110863","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}
引用次数: 0
Glucose-lipid metabolic index reflects cognitive impairment of non-diabetic elderly individuals. 糖脂代谢指数反映非糖尿病老年人的认知功能障碍。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251352548
Yeting Zeng, Xiangteng Zhao, Shaoming Sang, Shiwen Yu, Chunjiu Zhong
{"title":"Glucose-lipid metabolic index reflects cognitive impairment of non-diabetic elderly individuals.","authors":"Yeting Zeng, Xiangteng Zhao, Shaoming Sang, Shiwen Yu, Chunjiu Zhong","doi":"10.1177/13872877251352548","DOIUrl":"https://doi.org/10.1177/13872877251352548","url":null,"abstract":"<p><p>BackgroundGlucose and lipid metabolic disorders are involved in the impairment of cognitive function. However, it remains unclear the link between a new indicator of glucose-lipid metabolism index (GLMI) and cognitive impairment.ObjectiveThis study investigates the relationship between GLMI and multidimensional cognitive function in adults aged ≥ 60 years.MethodsGLMI was derived from glucose and lipid metabolism parameters. Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning test, Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST) were used to evaluate the cognitive abilities of participants. Linear regression, subgroup analyses, multivariable adjustments, and restricted cubic spline (RCS) models were employed to evaluate GLMI-cognition associations.ResultsAmong 787 participants from NHANES 2011-2014, diabetic individuals exhibited higher GLMI levels and more severe cognitive impairment than non-diabetic counterparts. In non-diabetic adults, GLMI showed linear correlations with CERAD and DSST assessed cognitive deficits. Subgroup analyses confirmed high GLMI as an independent risk factor for cognitive dysfunction in CERAD and DSST assessment. Multivariable regression revealed increased GLMI significantly elevated cognitive decline risk. ROC analysis identified 581.41 as the optimal GLMI cutoff (specificity: 86.0%) for predicting DSST impairment, outperforming traditional indices (TyG/HOMA-IR). RCS models demonstrated nonlinear GLMI-cognition associations, with a dose-dependent risk curve (200-800 range) and critical threshold at 545.ConclusionsThis study establishes that a high score of GLMI is associated with great severity of cognitive impairment in non-diabetic population.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352548"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540287","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}
引用次数: 0
An ABCA1 missense variant decreases cholesterol efflux and confers Alzheimer's disease risk in the Chinese population. ABCA1错义变异体降低胆固醇外排,增加中国人患阿尔茨海默病的风险。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 DOI: 10.1177/13872877251350722
Sze Kei Liu, Han Cao, Xin Yang, Xiaopu Zhou, Yu Chen, Wing-Yu Fu, San Yuen Chan, Fanny Cf Ip, Kin Y Mok, Vincent Ct Mok, Timothy Cy Kwok, John Hardy, Amy Ky Fu, Nancy Y Ip
{"title":"An <i>ABCA1</i> missense variant decreases cholesterol efflux and confers Alzheimer's disease risk in the Chinese population.","authors":"Sze Kei Liu, Han Cao, Xin Yang, Xiaopu Zhou, Yu Chen, Wing-Yu Fu, San Yuen Chan, Fanny Cf Ip, Kin Y Mok, Vincent Ct Mok, Timothy Cy Kwok, John Hardy, Amy Ky Fu, Nancy Y Ip","doi":"10.1177/13872877251350722","DOIUrl":"https://doi.org/10.1177/13872877251350722","url":null,"abstract":"<p><p>BackgroundGenetic studies have revealed that single-nucleotide polymorphisms (SNPs) of <i>ABCA1</i> are associated with Alzheimer's disease (AD) risk. However, their AD-related effects in non-European populations are not well studied. Moreover, the functional implications of these AD-associated SNPs remain unclear.ObjectiveWe examined the AD associations of <i>ABCA1</i> SNPs in the Chinese population and investigated the underlying mechanisms whereby these SNPs modulate AD risk.MethodsWe conducted a genetic analysis in a Hong Kong Chinese AD cohort (<i>n</i> = 332 patients with AD, <i>n</i> = 316 normal controls). Specifically, we analyzed 6 independent <i>ABCA1</i> SNPs reported to be associated with AD risk in populations of European descent. To investigate the effects of these SNPs on ABCA1 protein function and brain molecular phenotypes, we analyzed cholesterol efflux in human glioblastoma cells as well as the associations between the AD risk SNPs and brain transcriptomic profiles, respectively.ResultsThe <i>ABCA1</i> coding SNP, rs2230806 (p.R219 K), was significantly associated with AD in the Chinese population, specifically in females (odds ratio [95% confidence interval] = 1.65 [1.16-2.33]). Notably, human glioblastoma cells expressing the <i>ABCA1</i> R219 K showed a 17% cholesterol efflux reduction (<i>p</i> < 0.001). Moreover, <i>ABCA1</i> rs2230806 was associated with changes in the expression of oligodendrocyte genes involved in myelination in the brain in females.ConclusionsWe identified a significant AD risk <i>ABCA1</i> coding variant in the Chinese population and demonstrated its effects on cholesterol efflux and brain molecular phenotypes. These results shed light on the genetic basis whereby an <i>ABCA1</i> genetic variant contributes to AD pathogenesis.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251350722"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540286","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}
引用次数: 0
Immunocal®, a cysteine-rich whey protein, rescues reelin and reduces amyloid plaque burden in a transgenic amyloid-β protein precursor (hAβPPSweInd) mouse model of Alzheimer's disease. Immunocal®是一种富含半胱氨酸的乳清蛋白,可在转基因淀粉样蛋白-β蛋白前体(hAβPPSweInd)小鼠阿尔茨海默病模型中拯救reelin并减轻淀粉样斑块负担。
IF 3.4 3区 医学
Journal of Alzheimer's Disease Pub Date : 2025-07-01 Epub Date: 2025-05-05 DOI: 10.1177/13872877251338323
Alexandra Sandberg, Srivalli Puttagunta, Nathan Duval, Holly Fleming, Lilia Koza, Kade Hieber, Jessica Holsopple, Michael Reyna, Daniel Paredes, Daniel A Linseman
{"title":"Immunocal<sup>®</sup>, a cysteine-rich whey protein, rescues reelin and reduces amyloid plaque burden in a transgenic amyloid-β protein precursor (hAβPP<sub>SweInd</sub>) mouse model of Alzheimer's disease.","authors":"Alexandra Sandberg, Srivalli Puttagunta, Nathan Duval, Holly Fleming, Lilia Koza, Kade Hieber, Jessica Holsopple, Michael Reyna, Daniel Paredes, Daniel A Linseman","doi":"10.1177/13872877251338323","DOIUrl":"10.1177/13872877251338323","url":null,"abstract":"<p><p>BackgroundDeficits in Reelin expression play a significant role in the pathogenesis of various neurological disorders, including schizophrenia and Alzheimer's disease (AD). Notably, Reelin-expressing neurons of the entorhinal cortex layer II are among the first to be affected in AD.ObjectiveStrategies aimed at correcting deficits in Reelin might provide a novel therapeutic approach for AD.MethodsHere, we examined the effects of the whey protein supplement and glutathione (GSH) precursor, Immunocal<sup>®</sup>, on Reelin expression both in vitro in hippocampal-entorhinal cortex slices from rat brain and in vivo in the hAβPP<sub>SweInd</sub> (J20) mouse model of AD<i>.</i>ResultsIncubation of brain slices with Immunocal<sup>®</sup> increased Reelin expression at the mRNA and protein levels. Oral treatment with Immunocal<sup>®</sup>, given <i>ad libitum</i> in drinking water beginning at 3 months of age, corrected a deficit in cortical GSH levels observed in untreated mice and preserved Reelin expression in the hippocampal-entorhinal cortex sub-region of 5-month-old J20 mice. We also assessed the long-term effects of Immunocal<sup>®</sup> by treating J20 mice from 3 months old to 12 months old. Long-term Immunocal<sup>®</sup> treatment preserved brain GSH and rescued Reelin mRNA and protein expression, while significantly reducing amyloid plaque formation in the entorhinal cortex and hippocampus of AD mice.ConclusionsThese findings suggest that Immunocal<sup>®</sup> promotes Reelin expression in vitro and sustains brain GSH and Reelin expression while diminishing amyloid plaque load in the entorhinal cortex and hippocampus of J20 mice. Thus, Immunocal<sup>®</sup> offers a promising therapeutic approach to enhance Reelin expression and curtail amyloid deposition in AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"94-110"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021059","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}
引用次数: 0
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