Journal of Alzheimer's Disease最新文献

{"title":"Plasma leptin, resistin, tumor necrosis factor-alpha, and interleukin-6 with risk of dementia: A prospective population study.","authors":"Peiqi Zhang, Nianwei Wu, Qingping Xue, Jingyi Li, Qingqing Ouyang, Xinyue Yu, Yunhaonan Yang, Yidan Dong, Fan Li, Tianlei Wang, Shuo Li, Xiong-Fei Pan","doi":"10.1177/13872877251352480","DOIUrl":"https://doi.org/10.1177/13872877251352480","url":null,"abstract":"<p><p>BackgroundAdipokines secreted from adipose tissue may contribute to dementia pathogenesis.<b>Objective:</b> Our study investigated the associations between plasma levels of leptin, resistin, TNF-α, and IL-6 and the risk of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD).MethodsPlasma protein levels were measured using the Olink Proximity Extension Assay, and dementia was ascertained from hospital admissions and death registries in the UK Biobank. Multivariable Cox proportional hazards models with stepwise covariate adjustments were used to assess associations. Subgroup analyses were conducted to examine whether the associations differed by sociodemographic characteristics, lifestyle factors, and major diseases.ResultsAmong 32,002 participants, 793 developed all-cause dementia, including 260 with AD and 96 with VaD. Plasma levels of resistin and IL-6 were positively associated with risks of all-cause dementia, with hazard ratios (95% confidence intervals) of 1.10 (1.03, 1.18) and 1.10 (1.04, 1.17), respectively. Leptin (0.98; 0.86, 1.12) and TNF-α levels (1.06; 0.98, 1.13) were not significantly associated with all-cause dementia. Resistin (1.28; 1.08, 1.53) and TNF-α levels (1.21; 1.04, 1.40) were associated with VaD risk. There was a lack of evidence for the associations between four adipokines and AD. Subgroup analyses showed stronger associations between resistin and all-cause dementia in those with high body mass index, diabetes, or stroke.ConclusionsPlasma levels of resistin and IL-6 were positively associated with risks of all-cause dementia, with resistin and TNF-α strongly linked to VaD. These findings support a potential role of adipokines in dementia pathogenesis, particularly for VaD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352480"},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540303","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":"Association between atherogenic index of plasma and dementia: A longitudinal observational study.","authors":"Jie Lin, Yan Li, Hao Li","doi":"10.1177/13872877251339841","DOIUrl":"10.1177/13872877251339841","url":null,"abstract":"<p><p>BackgroundAtherogenic index of plasma (AIP) is a novel biomarker for status of lipid metabolism, but the association between AIP and dementia remains unclear.ObjectiveWe aimed to investigate the association between AIP and dementia among people with different glycemic status.MethodsFrom the China Health and Retirement Longitudinal Study, 5195 dementia-free adults aged ≥45 (mean age 62.15 ± 7.00 years; 2668 [51.36%] female) at baseline (2011-2012) were followed up until 2018 to detect incident dementia. Dementia was ascertained based on cognitive batteries and the Activity of Daily Living scale. AIP was calculated by the formula: log [triglyceride (mg/dL) / high-density lipoprotein cholesterol (mg/dL)] and tertiled as low, moderate, and high. Data were analyzed using logistic regression.ResultsDuring the follow-up, 716 (13.3%) participants developed dementia. In basic-adjusted model, higher AIP was dose-dependently associated with an increased risk of dementia (per 1-SD increment in AIP, odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.02, 1.20, p = 0.020), whereas the association was not significant in fully-adjusted model (OR: 1.07 [0.97, 1.18]; p = 0.158). Compared with low AIP group, the OR (95% CI) of dementia was 1.27 (1.01, 1.60) for high AIP. After stratification, the association between high AIP and dementia was significant among people with diabetes (OR: 1.97, 95% CI: 1.11, 3.49) and a significant multiplicative interaction between high AIP and glycemic status was found (p for interaction = 0.029).ConclusionsHigh AIP is associated with higher risk of dementia, particularly among people with diabetes. Our findings suggested that AIP could serve as an early indicator of dementia.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"197-205"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967526","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":"¹⁸F-FDG PET for the differential diagnosis of Alzheimer's disease and frontotemporal lobar degeneration: A multicenter prospective study in Japan.","authors":"Kengo Ito, Yukihiko Washimi, Takashi Kato, Keisuke Suzuki, Yasuomi Ouchi, Chigusa Watanabe, Yoshihide Sunada, Yumiko Kutoku, Kazunari Ishii, Kenji Ishii, Michio Kitayama, Etsuro Matsubara, Noriyuki Kimura, Harumasa Takano, Hiroaki Adachi, Kazuhiro Hara, Takeshi Kawarabayashi, Mikio Shoji, Norio Sugimoto","doi":"10.1177/13872877251338691","DOIUrl":"10.1177/13872877251338691","url":null,"abstract":"<p><p>Background¹⁸F-fluoro-2-deoxy-2-D-glucose positron emission tomography (¹⁸F-FDG PET) is a biomarker of neuronal injury, according to the revised National Institute on Aging-Alzheimer's Association criteria.ObjectiveThis multicenter prospective cohort study aimed to evaluate the value of ¹⁸F-FDG PET for differential diagnosis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) in comparison with phosphorylated tau protein (p-tau181) in cerebrospinal fluid (CSF).MethodsIn total, 138 patients (AD, 119; FTLD, 19) from 11 participating institutions underwent clinical and neuropsychological examinations, magnetic resonance imaging (MRI), CSF examination, and ¹⁸F-FDG PET at baseline. The cases were visually classified into predefined dementia patterns using ¹⁸F-FDG PET by three experts. A region-of-interest (ROI)-based automated analysis of ¹⁸F-FDG PET was also performed. The participants were followed up for 12 months, and the clinical diagnosis of dementia was re-evaluated.ResultsThe sensitivity, specificity, and accuracy of the visual reading of¹⁸ F-FDG PET for differentiating AD from FTLD were 94%, 78%, and 92%, respectively. In contrast, those of p-tau181 in CSF were 62%, 79%, and 65%, respectively. The sensitivity, the primary endpoint, was 32% higher for ¹⁸F-FDG PET than for p-tau181 in CSF. Additionally, the accuracy, the secondary endpoint, was 27% higher for ¹⁸F-FDG PET than for p-tau181 in CSF. In addition to the visual reading of ¹⁸F-FDG PET, the ROI-based automated analysis showed sensitivity, specificity, and accuracy of 81%, 79%, and 81%, respectively.ConclusionsThis study showed that the diagnostic performance of ¹⁸F-FDG PET in differential diagnosis of AD and FTLD was higher than that of p-tau181 in CSF.Trial registrationUMIN-CTR (UMIN 000016427, https://www.umin.ac.jp/ctr/) and Japan Registry of Clinical Trials (jRCTs041180098, https://jrct.mhlw.go.jp/).</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"293-303"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967132","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":"Evaluation of early-phase ¹⁸F-Florbetaben PET as a surrogate biomarker of neurodegeneration: In-depth comparison with ¹⁸F-FDG PET at group and single patient level.","authors":"Jose Antonio Lojo-Ramírez, Paula Fernández-Rodríguez, Miriam Guerra-Gómez, Alba Marta Marín-Cabañas, Emilio Franco-Macías, Jose Manuel Jiménez-Hoyuela-García, David García-Solís","doi":"10.1177/13872877251340380","DOIUrl":"10.1177/13872877251340380","url":null,"abstract":"<p><p>BackgroundImaging biomarkers are essential in Alzheimer's disease (AD) diagnosis, particularly since the introduction of the ATN criteria by the NIA-AA. These criteria include amyloid-β plaques (amyloid PET), fibrillar tau (tau PET), and neurodegeneration (FDG PET or MRI). Early-phase amyloid PET imaging has shown a strong correlation with FDG PET at the group level.ObjectiveThis study evaluates the comparability of early-phase FBB PET (eFBB) perfusion imaging and FDG PET metabolic imaging at both group and individual levels.MethodsA retrospective study included 103 patients with mild cognitive impairment (MCI) or mild dementia suspected of AD who underwent FDG PET and dual-phase ¹⁸F-Florbetaben PET (including a 5-min eFBB scan) between 2019 and 2023, along with 33 healthy controls. Imaging analyses included qualitative, semi-quantitative, and voxel-wise techniques to compare eFBB and FDG PET scans.ResultseFBB and FDG PET SUVR values showed a strong correlation across all brain regions (rho = 0.879). Visual assessments of eFBB and FDG PET by two raters achieved intra-observer agreement rates of 87.5% and 86.4%, respectively. Voxel-wise analysis revealed moderate to good overlap, as indicated by Dice-Sørensen coefficients, in the MCI and mild dementia groups. Discriminative performance between eFBB and FDG PET was comparable, with no significant differences as eFBB reliably reflected brain metabolic patterns observed on FDG PET, supporting its diagnostic utility.ConclusionseFBB PET could serve as a surrogate biomarker for FDG PET in the diagnostic evaluation of neurodegenerative dementias. Dual-phase amyloid PET enables simultaneous assessment of neurodegeneration and amyloid burden, offering a streamlined and resource-efficient approach for clinical practice.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"304-316"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966671","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":"Sleep disturbances and disorders in the memory clinic: Self-report, actigraphy, and polysomnography.","authors":"Aaron Lam, Dexiao Kong, Angela L D'Rozario, Catriona Ireland, Rebekah M Ahmed, Zoe Menczel Schrire, Loren Mowszowski, Johannes Michaelian, Ron R Grunstein, Sharon L Naismith","doi":"10.1177/13872877251338065","DOIUrl":"10.1177/13872877251338065","url":null,"abstract":"<p><p>BackgroundSleep disturbances are common in dementia but rarely studied in memory clinics.ObjectiveIn a memory clinic setting we aimed to (1) identify rates of obstructive sleep apnea (OSA), abnormal sleep duration, circadian phase shift, insomnia, poor sleep quality, and REM sleep behavior disorder (RBD); (2) assess concordance between self-reported and actigraphy-derived measures; investigate associations between sleep disturbances; and (3) neuropsychological performance and (4) cognitive status.MethodsAdults over 50 at a memory clinic between 2009-2024 were included. OSA was assessed via polysomnography and prior history. Sleep duration and circadian phase were measured by self-report and actigraphy. Self-report questionnaires evaluated insomnia, sleep quality, and RBD. Global cognition, processing speed, memory, and executive function were assessed. Analysis of Covariance and multinomial logistic regression examined the impact of OSA, sleep duration, insomnia, and sleep quality on cognition and cognitive status.Results1234 participants (Mage 67.2, 46%M) were included. 75.3% had OSA, while 12.7% were previously diagnosed. Insomnia affected 12.0%, 54.3% had poor sleep quality, and 14.2% endorsed RBD symptoms. Self-reported short (30.5%) and long (10.2%) sleep exceeded actigraphy rates (8.5% and 5.1%) with poor concordance between measures. OSA was linked to impaired global cognition and memory (p < 0.05). Prolonged sleep predicted deficits in global cognition, processing speed, memory, and executive function and a higher risk of aMCI (all p < 0.05). Poor sleep quality was linked to better memory (p < 0.05).ConclusionsDespite discrepancies between self-reported and objective prevalence rates, sleep disturbances are highly prevalent in memory clinics and impact cognition, necessitating further examination.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"78-93"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965543","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":"<i>Codonopsis pilosula</i> polysaccharides alleviate neuronal apoptosis induced by endoplasmic reticulum stress-activated PERK-ATF4-CHOP signaling in APP/PS1 mice.","authors":"Yuanqin Cai, Xi Wang, Yang Xiang, Zhenning Wang, Qinghua Long, Chuhua Zeng","doi":"10.1177/13872877251339484","DOIUrl":"10.1177/13872877251339484","url":null,"abstract":"<p><p>Background<i>Codonopsis polysaccharides</i> (CPPs) shows neuroprotective potential in Alzheimer's disease (AD) and may reduce neuronal apoptosis by modulating endoplasmic reticulum stress (ERS).ObjectiveTo investigate the protective mechanisms of CPPs against neuronal apoptosis in APP/PS1 mice, focusing on the ERS response and the PERK-ATF4-CHOP signaling pathway.MethodsAPP/PS1 mice were orally administered CPPs at different doses. Their learning and memory abilities were evaluated using the Morris water maze (MWM). The integrity of hippocampal neurons and senile plaque deposition were assessed using histopathology, immunohistochemistry, and immunofluorescence. The expression of amyloid-β (Aβ) plaques secretase protein, ERS markers, and apoptosis-related proteins was assessed using western blot analyses. The affinity of the PERK-ATF4-CHOP pathway and CPPs was analyzed and assessed using molecular docking.ResultsMWM testing revealed that CPPs improved the learning and memory abilities of APP/PS1 mice. Histopathological examination confirmed that CPPs reduced hippocampal neuronal apoptosis. Immunohistochemistry and immunofluorescence analysis showed that CPPs decreased Aβ protein expression and ERS. Western blot analysis further confirmed that CPPs reduced the expression of proteins related to Aβ synthesis; downregulated the expression of glucose-regulated protein 78 (GRP78), PERK, ATF4, CHOP, and Bcl-2 associated X protein (Bax), while upregulating the expression of B-cell lymphoma 2 (Bcl-2).ConclusionsThis study demonstrates that CPPs exert neuroprotective effects by targeting the PERK-ATF4-CHOP signaling pathway and alleviating ERS, suggesting a novel approach and potential therapeutic agent for AD treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"317-330"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993629","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 critical examination of the relationship between cardiovascular health, cognition, and dementia risk.","authors":"Joshua L Gills, Omonigho M Bubu","doi":"10.1177/13872877251337776","DOIUrl":"10.1177/13872877251337776","url":null,"abstract":"<p><p>Poor cardiovascular health is strongly linked to increased risk of cognitive impairment and Alzheimer's disease and related dementias. This commentary discusses Yang and associates' work on the associations between cardiovascular health in middle age, as defined by Life Essential 8 scores, and later digital cognitive performance and incident Alzheimer's disease. We examine the strengths and weaknesses of their study within the broader research context. We emphasize the potential significance of sleep and stress the need for longitudinal studies incorporating robust neuropsychiatric methodologies, advanced neuroimaging techniques, and diverse participant samples to enhance the reliability and generalizability of results.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"44-46"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007182","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":"Differential effects of antidepressants on cognition in Alzheimer's disease with depression: A sub-group analysis of an open-label, observational study.","authors":"Eduardo Cumbo, Daniela Migliore","doi":"10.1177/13872877251340084","DOIUrl":"10.1177/13872877251340084","url":null,"abstract":"<p><p>BackgroundDepressive symptoms are common in Alzheimer's disease (AD), leading to an increasing use of antidepressants.ObjectiveTo compare the effects of vortioxetine with other conventional antidepressants on cognition in AD patients with depressive symptoms.MethodsThis analysis is a subgroup of a 12-month, prospective, randomized, open-label, parallel-group study involving 108 outpatients receiving either vortioxetine or escitalopram, paroxetine, or bupropion as part of routine care. Data were collected at baseline, 6 and 12 months. Cognitive symptoms were assessed using the Mini-Mental State Examination (MMSE), Attentive Matrices (AM), Coloured Progressive Matrices (CPR), and Digit Span; depressive symptoms using the Hamilton Depression Scale (HAM-D) and the Cornell Scale for Depression in Dementia (CSDD). Results for patients on vortioxetine were compared to those on other antidepressants.ResultsTotal scores on cognitive measures improved in all groups. Improvements versus baseline in MMSE, AM, and CPM were statistically significant in the vortioxetine group (p < 0.001), but not in the other antidepressant groups. Digit Span scores did not differ significantly from baseline. The between-group differences in MMSE, AM, and CPM changes were statistically significant in favor of vortioxetine (p < 0.05), while the Digit Span change showed a trend towards superiority with vortioxetine, but did not reach statistical significance. The between-group differences in HAM-D and CSDD changes were also statistically significant for vortioxetine (p < 0.05).ConclusionsVortioxetine was superior in improving both cognitive and depressive symptoms compared to other antidepressants. Larger studies which may also help to understand whether the beneficial effect observed with vortioxetine was a direct effect or mediated by its specific antidepressant efficacy are required.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"271-279"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007186","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":"Identification of NDUFV2, NDUFS7, OPA1, and NDUFA1 as biomarkers for Alzheimer's disease: Insights from oxidative stress and mitochondrial dysfunction in the hippocampus.","authors":"Junshi Zhang, Tingting Liu, Haojie Wu, Jianshe Wei, Qiumin Qu","doi":"10.1177/13872877251339771","DOIUrl":"10.1177/13872877251339771","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is characterized by amyloid-β deposits, neurofibrillary tangles, and hippocampal neurodegeneration, with oxidative stress and mitochondrial dysfunction playing critical roles in its pathogenesis. Identifying hub genes associated with these processes could advance biomarker discovery and therapeutic strategies.ObjectiveThis study aimed to identify key oxidative stress- and mitochondrial dysfunction-related genes in the AD hippocampus, evaluate their diagnostic potential, and explore therapeutic agents targeting these genes.MethodsWe analyzed datasets GSE48350 and GSE5281, encompassing 56 controls and 29 AD patients. Weighted gene co-expression network analysis (WGCNA) selected genes with significance (adjusted <i>p</i>-value < 0.05 and |logFC| ≥ 0.5). Further studies involved immune cell infiltration, Gene set enrichment analysis (GSEA), and intersecting differentially expressed genes (DEGs) with oxidative stress-related genes (ORGs) and mitochondrial dysfunction-related genes (MDRGs). Functional enrichment and Protein-protein interaction (PPI) analyses were conducted. Experimental validation was done in AD mouse models, and diagnostic potential was tested using datasets GSE28146 and GSE29652. Therapeutic drugs were predicted based on hub genes.ResultsAD showed altered immune cell expression. GSEA linked DEGs to nervous system processes and neurotransmitters. 194 oxidative stress-related DEGs were enriched in neuronal death and mitochondrial processes. PPI analysis identified 24 DEGs related to both oxidative stress and mitochondrial dysfunction (DEO-MDRGs), with diagnostic potential (AUC > 0.5). LASSO regression selected four DEO-MDRGs: NDUFV2, NDUFS7, OPA1, and NDUFA1. Their protein levels were reduced in AD mice with decreased mitochondrial function. These genes showed good diagnostic performance. Potential drugs, like ME-344 and metformin hydrochloride, may be useful in AD treatment.ConclusionsNDUFV2, NDUFS7, OPA1, and NDUFA1 can serve as biomarkers for AD diagnosis.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"167-183"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025382","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":"Low-dose dietary vorinostat increases brain histone acetylation levels and reduces oxidative stress in an Alzheimer's disease mouse model.","authors":"Chhanda Bose, Ashly Hindle, Shane C Smith, Jake Strickland, Charlie Zhang, Isabel Guzman, Adam Baker, Igor Ponomarev, Maria Manczak, Andrew C Shin, Ranadip Pal, Sharda P Singh, J Josh Lawrence","doi":"10.1177/13872877251352107","DOIUrl":"https://doi.org/10.1177/13872877251352107","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) disrupts histone acetylation/deacetylation homeostasis, blocking access of transcription factors to DNA, and compromising learning. Vorinostat (VOR), the only FDA-approved HDAC inhibitor that is orally bioavailable and brain penetrant, confers neuroprotection in AD models. We delivered VOR via diet in an AD mouse model, examining tolerability, accompanied by biochemical analyses.ObjectiveOur objective was to examine dietary delivery of vorinostat for tolerability, including changes to histone acetylation, amyloid-β (Aβ) production, oxidative stress (OS), mitochondrial health, and synaptic integrity.MethodsFood pellets containing control, 0.18 mg/g (low-dose) and 0.36 mg/g (high-dose) VOR were administered to hAβ-KI AD mice for 14 days. Brain acetyl-histone H3 (AH3), total H3 expression, and synaptic markers were measured via Western blot. Aβ, H₂O₂, antioxidant capacity, lipid peroxidation (via 4-hydroxynonenal (4-HNE)), adenosine triphosphate (ATP), and citrate synthase (CS) activity were measured in brain tissue.ResultsVOR inhibited brain HDAC enzyme activity and increased AH3 and H3 expression at both VOR doses. Aβ and synaptic proteins were not significantly affected; however, OS markers were improved at both doses. Both doses increased CS activity, while ATP was increased only at the low dose. Finally, low-dose VOR was tolerable over 2 months.ConclusionsWe established that low-dose VOR, delivered via diet, is tolerable in AD mice, successfully inhibiting brain HDAC activity while reducing OS and improving mitochondrial health. This study improves existing preclinical experimental designs by enabling noninvasive manipulation of histone acetylation through dietary intervention. This route of administration provides advantages for future preclinical animal studies.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352107"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540302","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}