Journal of Alzheimer's disease reports最新文献

{"title":"Cardio and cerebrovascular diseases risk among Alzheimer's disease patients and racial/ethnic disparities, based on Hawaii Medicare data.","authors":"Chathura Siriwardhana, Enrique Carrazana, Kore Liow, John J Chen","doi":"10.1177/25424823241289038","DOIUrl":"10.1177/25424823241289038","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and cardiovascular and cerebrovascular diseases (CVD) are significant concerns among the elderly, sharing overlapping risk factors. Hawaii's unique demographic profile, characterized by its strong ethnic diversity, shows marked racial health disparities. For instance, the Native Hawaiian/Pacific Islander (NHPI) population is identified as a high-risk group for multiple health conditions, including CVD.</p><p><strong>Objective: </strong>This study investigates the impact of AD on the risk of developing CVD, with a focus on racial influences, utilizing Hawaii Medicare data.</p><p><strong>Methods: </strong>Employing nine years of longitudinal Hawaii Medicare data, this study identified elderly patients diagnosed with AD who subsequently developed heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), acute myocardial infarction (AMI), or stroke. To assess the risk of CVD, we utilized multistate models and employed propensity score-matched controls. Additionally, we evaluated racial and ethnic differences in the risk of these diseases, while accounting for other relevant risk factors.</p><p><strong>Results: </strong>Our findings revealed an elevated risk of AMI, HF, and IHD among individuals diagnosed with AD. Additionally, socioeconomic status (SE) was identified as a crucial factor in the risk of cardio and cerebrovascular diseases. Within the low SE group, NHPIs exhibited increased risks of HF and IHD compared to their white counterparts. Interestingly, NHPIs demonstrated reduced risks of HF in the higher SE group.</p><p><strong>Conclusions: </strong>The presence of AD increases the likelihood of developing AMI, HF, and IHD. Moreover, the risk of CVD appears to be influenced by race/ethnicity in Hawaii, as well as socioeconomic status.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1529-1540"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring for dose optimization in Alzheimer's disease and in dementia with Lewy bodies: A randomized single-blinded clinical trial.","authors":"Michael Hén Forbord Fischer, Ivan Chrilles Zibrandtsen, Peter Johannsen, Volkert Siersma, Jan Borg Rasmussen, Jens Borggaard Larsen, Peter Høgh","doi":"10.1177/25424823241289373","DOIUrl":"10.1177/25424823241289373","url":null,"abstract":"<p><strong>Background: </strong>Previous evidence suggests serum concentrations of donepezil varies in clinical populations and that a dose higher than standard may have additional positive effect on cognition. Therapeutic drug monitoring (TDM) is a tool for dose optimization (DO) whereby treatment is adjusted based on previous quantification of the prescribed drug.</p><p><strong>Objective: </strong>Investigate whether TDM-based DO of donepezil or memantine improves clinical outcomes and/or reduce the frequency of adverse reactions (ARs) in neurodegenerative conditions commonly treated with these two study drugs.</p><p><strong>Methods: </strong>Single-blinded 1:1 randomized controlled study in an outpatient memory clinic. Eligible participants either newly diagnosed with Alzheimer's disease dementia (AD), dementia with Lewy bodies (DLB), or Parkinson's disease dementia (PDD) scheduled for treatment with donepezil or memantine. The intervention group received TDM based DO. The control group received DO solely based on clinical assessment. Clinical outcomes were change in Mini-Mental State Examination, Addenbrooke's Cognitive Examination, Neuropsychiatric Inventory, and Disability Assessment in Dementia from baseline to 12 months. Additionally, data on incidence and severity of ARs and proportion of participants with a serum concentration within the therapeutic reference range were collected.</p><p><strong>Results: </strong>132 participants recruited (125 AD, 7 DLB, none with PDD) of whom 107 completed the study (101 AD and 6 DLB), fewer in the control group than planned. Statistical analysis did not reveal significant differences between groups neither for clinical outcomes nor for frequency of ARs.</p><p><strong>Conclusions: </strong>TDM based DO did not significantly improve clinical outcomes nor reduce the frequency of ARs albeit important caveats to the results apply.</p><p><strong>Clincialtrialsgov identifier: </strong>NCT04117178 (first posted October 7, 2019).</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1516-1528"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying shared diagnostic genes and mechanisms in vascular dementia and Alzheimer's disease via bioinformatics and machine learning.","authors":"Wanning Zheng, Dongdong Lin, Shunan Shi, Jiayi Ren, Jiong Wu, Ming Wang, Shu Wan","doi":"10.1177/25424823241289804","DOIUrl":"10.1177/25424823241289804","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and vascular dementia (VaD) share overlapping pathophysiological characteristics, yet comparative genetic studies are rare. Understanding these overlaps may aid in identifying common diagnostic markers and therapeutic targets.</p><p><strong>Objective: </strong>This study identifies shared diagnostic genes and mechanisms linking AD and VaD.</p><p><strong>Methods: </strong>Datasets GSE5281 and GSE122063 from the GEO database were used to identify differentially expressed genes (DEGs). Intersection DEGs were analyzed using KEGG and GO enrichment to explore signaling pathways. A PPI network was constructed, and LASSO and SVM-RFE were applied to identify core genes. CIBERSORT assessed immune cell composition and their relationship with core genes. Diagnostic efficacy was evaluated using ROC curves, nomogram, and Decision Curve Analysis (DCA). Core genes were used to identify characteristic genes in various brain regions of AD patients.</p><p><strong>Results: </strong>The analysis identified 9021 DEGs for AD and 373 DEGs for VaD, with 74 co-expressed genes and 8 core genes. ROC curves, nomogram, and DCA indicated high diagnostic accuracy. Core gene analysis revealed differential expression of characteristic genes in various brain regions of AD patients.</p><p><strong>Conclusions: </strong>This research identified 74 co-expressed genes and 8 pivotal diagnostic genes. These genes likely play roles in signal transduction, neuroinflammation, and autophagy in both AD and VaD. The findings offer potential targets for future research and clinical interventions. Further research should use larger, more diverse datasets and incorporate custom NGS panels to identify novel genetic variants, enhancing precise diagnostic and therapeutic strategies.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1558-1572"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous thrombolysis therapy and dementia risk in acute ischemic stroke patients: A retrospective cohort study in Taiwan.","authors":"Yan-Siang Huang, Te-Jung Kung, Yi-Fang Chuang","doi":"10.1177/25424823241292283","DOIUrl":"10.1177/25424823241292283","url":null,"abstract":"<p><strong>Background: </strong>Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke (AIS) to improve functional outcomes. Furthermore, AIS is an important risk factor for dementia. Limited evidence has shown the long-term benefit of IVT on dementia in Western countries.</p><p><strong>Objective: </strong>We aim to investigate the association between IVT and the risk of dementia in acute ischemic stroke patients in Asian population.</p><p><strong>Methods: </strong>A retrospective cohort study using medical records from a medical center in Taiwan between 2017 and 2022 was conducted. We included acute ischemic stroke patients aged over 55 years old who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained through dementia diagnosis in medical records. The inverse probability of treatment-weighted Cox proportional hazard models were used to estimate the association between IVT and incident dementia.</p><p><strong>Results: </strong>A total of 1471 patients with AIS were included. 939 (63.8%) were male, and the mean age was 70.7 <math><mspace></mspace> <mo>±</mo> <mspace></mspace></math> 9.6 years. Among them, 19.1% of patients (n = 281) received IVT. The mean follow-up time was 2.6 <math><mspace></mspace> <mo>±</mo> <mspace></mspace></math> 1.7 years. Although not statistically significant, the IVT was associated with a decreased risk of dementia (HR: 0.88 [95%CI 0.54-1.41)]).</p><p><strong>Conclusions: </strong>The IVT was associated with lower risk of dementia, although not statistically significant, in reducing the incidence of dementia in Asian patients with ischemic stroke. Studies with larger sample sizes will be needed in the future.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1541-1548"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential DNA methylation profiles of Alzheimer's disease-related genomic pathways in the blood of cognitively-intact individuals with and without high impact chronic pain.","authors":"Larissa J Strath, Lingsong Meng, Yutao Zhang, Asha Rani, Zhiguang Huo, Thomas C Foster, Roger B Fillingim, Yenisel Cruz-Almeida","doi":"10.1177/25424823241289376","DOIUrl":"10.1177/25424823241289376","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain and Alzheimer's disease (AD) are prevalent in older age and their etiologies remain to be understoodand evidence supports potential associations between the two. Both high impact pain and AD have been previously associated with differences in the epigenome. Interactions with the epigenome may serve as a possible underlying mechanism linking high impact pain and AD.</p><p><strong>Objective: </strong>To complete epigenetic canonical pathways analyses related to AD in individuals with and without high-impact knee pain.</p><p><strong>Methods: </strong>This manuscript aimed to explore differences in DNA methylation patterns in genes and pathways associated with AD. Blood samples of cognitively intact, community-dwelling adults with high impact knee painmversus pain-free controls were compared on their DNA methylation levels of AD-related genes. Pathway enrichment analysis was performed on significantly different DNA Methylation probes by pain group.</p><p><strong>Results: </strong>There were significant DNA methylation differences between the high impact versus the pain-free control groups in genes and pathways associated with AD (p < 0.05). We found a total of 17,563 differentially methylated CpG probes, including 13,411 hypermethylated CpG probes and 4152 hypomethylated CpG probes. Further, pathway analysis revealed these differences were significantly associated with AD-related pathways associated with AD progression.</p><p><strong>Conclusions: </strong>This study sample showed AD-related DNA methylation differences and associated potential canonical pathways in those with and without high impact knee pain. These results highlight the need to study overlapping epigenetic modifications underlying high impact pain and AD pathologies. Further studies, including gene expression, are needed to further explore the relationship between epigenetics, chronic pain, and AD.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1549-1557"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep brain stimulation of the nucleus basalis of Meynert in severe Alzheimer's disease.","authors":"Junpeng Xu, Bin Liu, Guosong Shang, Shuzhen Liu, Zhebin Feng, Haonan Yang, Di Liu, Qing Chang, Yuhan Chen, Xinguang Yu, Zhiqi Mao","doi":"10.1177/25424823241296780","DOIUrl":"10.1177/25424823241296780","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is increasingly prevalent, leading to severe cognitive decline and a diminished quality of life for patients. Nucleus basalis of Meynert deep brain stimulation (NBM-DBS) is a potential treatment approach.</p><p><strong>Objective: </strong>This study aims to assess the efficacy and safety of NBM-DBS for AD patients.</p><p><strong>Methods: </strong>We conducted a clinical study involving 6 patients with severe AD who received NBM-DBS. The treatment's safety and efficacy were evaluated using cognitive function tests (Mini-Mental State Examination, Montreal Cognitive Assessment, Alzheimer's Disease Rating Scale- cognitive subscale, Clinical Dementia Rating) and assessments of neuropsychiatric symptoms and sleep disorders (Functional Activity Questionnaire, Functional Independence Measure, Zarit Burden Interview, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Neuropsychiatric Inventory, Pittsburgh Sleep Quality Index).</p><p><strong>Results: </strong>NBM-DBS was safe, with no severe adverse events. It improved cognitive functions and self-care abilities without altering the disease's progression. Notably, NBM-DBS significantly alleviated neuropsychiatric symptoms and sleep disturbances.</p><p><strong>Conclusions: </strong>NBM-DBS could be a promising therapeutic approach for severe AD, particularly for managing neuropsychiatric symptoms and sleep disorders. Further research is warranted to confirm these preliminary findings.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1573-1586"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between activities and cognitive health: Stratified analysis by <i>APOE</i> ε4 status.","authors":"Yeonjung Jane Lee, Ernest Gonzales, Yanyan Wu, Kathryn L Braun, Peter Martin, Bradley Willcox, Ross Andel","doi":"10.1177/25424823241290528","DOIUrl":"10.1177/25424823241290528","url":null,"abstract":"<p><strong>Background: </strong>Despite the growing evidence on the modifiable and genetic factors associated with cognitive health, little is known about the role of the apolipoprotein E (<i>APOE</i>) gene ε4 allele in the associations between productive or leisure activities and cognitive health.</p><p><strong>Objective: </strong>This study fills a gap of knowledge by examining the associations among employment, civic engagement, and leisure activities and cognitive health by the presence of <i>APOE</i> ε4 allele, an established risk factor of Alzheimer's disease (AD).</p><p><strong>Methods: </strong>Using pooled data from the Health and Retirement Study (HRS) Psychosocial and Lifestyle Questionnaires (2010-2016) and the HRS data on <i>APOE</i> ε4 alleles, linear regression models with a lagged dependent variable were performed to examine associations between productive or leisure activities and cognitive functioning at the follow-up time point, as well as the role of <i>APOE</i> ε4 in these associations.</p><p><strong>Results: </strong>Among all participants, employment, low or high-intensity volunteering, and cognitive/social leisure activities were associated with higher levels of cognitive functioning. The presence of at least one ε4 allele was related to poorer cognitive functioning at the follow-up time point. Among people without the <i>APOE</i> ε4 allele, employment, high-intensity volunteering, and cognitive/social leisure activities were significantly associated with cognitive functioning. Among people with at least one <i>APOE</i> ε4 allele, low-intensity volunteering and cognitive/physical leisure activities were significantly associated with better cognitive functioning.</p><p><strong>Conclusions: </strong>We found that employment, civic engagement, and leisure activities all contribute to cognitive health, although the benefits may be restricted to low-intensity volunteering and cognitive/physical leisure activities among individuals with at least one <i>APOE</i> ε4 allele, who are known to be inherently at a greater risk of AD, highlighting an avenue to a relatively easily implementable strategy to promote cognitive health in this subpopulation.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1502-1515"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical evaluation of COSMIN scores in scales for mild cognitive impairment and Alzheimer's disease: A comprehensive review.","authors":"Xia Peng, Run-Chen Li, Ting Liang, Shi-Fen Xu, Yan Cao","doi":"10.1177/25424823241299023","DOIUrl":"10.1177/25424823241299023","url":null,"abstract":"<p><p><b>Background:</b> Timely diagnosis and intervention of mild cognitive impairment (MCI) can delay the development of Alzheimer's disease (AD). <b>Objective:</b> The purpose of this study was to analyze assessment tools for cognitive function using the Consensus Criteria for Selection of Health Measurement Instruments (COSMIN) method. Comparing the validity, reliability, and practicality of these assessment tools helps clinicians select appropriate assessment tools for patients, thereby improving diagnostic accuracy. <b>Methods:</b>We followed the updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and used the COSMIN checklist to conduct a thorough methodological quality assessment of the studies. The measurement properties were evaluated and rated on a scale from excellent to poor, based on adapted criteria. We then synthesized the best evidence by combining the COSMIN outcomes with the quality of findings to ensure a precise and comprehensive analysis. <b>Results:</b> We identified a total of 156 publications, which included 19 different cognitive assessment instruments. Among these, the Telephone version of the Cantonese Mini-Mental State Examination (T-CMMSE), the Montreal Cognitive Assessment (MoCA), and the Hong Kong versions of the MoCA (HK-MoCA-A1 and A2) demonstrated distinguished qualities. The assessment of measurement properties included internal consistency, reliability, validity, and sensitivity and specificity. Notably, the T-CMMSE showed superior methodological quality based on our rigorous analysis. <b>Conclusions:</b> The T-CMMSE, MoCA, and HK-MoCA-A1 and A2 were found to be notable cognitive assessment tools for MCI and AD. Future research should aim to expand on these findings by exploring a wider range of tools and contexts.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1596-1610"},"PeriodicalIF":2.8,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker Assessment in Parkinson's Disease Dementia and Dementia with Lewy Bodies by the Immunomagnetic Reduction Assay and Clinical Measures.","authors":"Giovanni R Malaty, Boris Decourt, Holly A Shill, Marwan N Sabbagh","doi":"10.3233/ADR-240110","DOIUrl":"10.3233/ADR-240110","url":null,"abstract":"<p><strong>Background: </strong>Plasma biomarker assays provide an opportunity to reassess whether Alzheimer's disease, Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB) plasma biomarkers are diagnostically useful.</p><p><strong>Objective: </strong>We hypothesized that immunomagnetic reduction (IMR) of plasma biomarkers could differentiate between patients with PDD and DLB and healthy patients when combined with established clinical testing measures.</p><p><strong>Methods: </strong>Plasma samples from 61 participants (12 PDD, 12 DLB, 37 controls) were analyzed using IMR to quantify amyloid-β 42 (Aβ₄₂), total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and α-synuclein (α-syn). Receiver operating characteristic curve (ROC) analysis was used to obtain sensitivity, specificity, and area under the ROC curve. Biomarker results were combined with clinical measures from the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Hoehn-Yahr stage to optimize diagnostic test performance.</p><p><strong>Results: </strong>Participants with PDD had higher α-syn than those with DLB and healthy participants and were distinguishable by their biomarker products Aβ₄₂×p-tau181 and Aβ₄₂×α-syn. Patients with DLB had higher p-tau181 than those with PDD and healthy participants and were distinguishable by their concentrations of α-syn×p-tau181. Plasma α-syn plus UPDRS versus either test alone increased sensitivity, specificity, and AUC when healthy patients were compared with those with PDD and DLB. Combined clinical examination scores and plasma biomarker products demonstrated utility in differentiating PDD from DLB when p-tau181 was combined with UPDRS, α-syn was combined with UPDRS, and α-syn×p-tau181 was combined with UPDRS.</p><p><strong>Conclusions: </strong>In this pilot study, IMR plasma p-tau181 and α-syn may discriminate between PDD and DLB when used in conjunction with clinical testing.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1361-1371"},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte dysfunction alters GABAergic communication and ammonia metabolism in the streptozotocin-induced sporadic Alzheimer's disease model.","authors":"Éverton Carlos Brezolin, Vitor Gayger-Dias, Vanessa-Fernanda Da Silva, Anderson Cigerce, Bruna Schultz, Thomas Michel Sobottka, Patrícia Nardin, Adriano Martimbianco de Assis, Marina Concli Leite, André Quincozes-Santos, Larissa Daniele Bobermin, Carlos-Alberto Gonçalves","doi":"10.1177/25424823241289036","DOIUrl":"10.1177/25424823241289036","url":null,"abstract":"<p><strong>Background: </strong>In the sporadic model of Alzheimer's disease (AD), induced by intracerebroventricular streptozotocin (STZ) administration, cognitive impairment is accompanied by specific astrocytic changes in the hippocampus prior to amyloid deposition.</p><p><strong>Objective: </strong>Hypothesizing that the synthesis of GABA, via MAO-B, contributes to ammonia elevation, thereby compromising antioxidant defense and ATP synthesis, and possibly contributing to cognitive damage, we determined the hippocampal levels of glutamine synthetase (GS), monoamine oxidase B (MAO-B) and other enzymes related to GABA metabolism.</p><p><strong>Methods: </strong>Immunoblotting and RT-PCR assays were carried out in hippocampal samples of Wistar rats, at 4 and 16 weeks post-STZ, in the sporadic STZ-induced AD model, corresponding to the pre-amyloid and amyloid phases, respectively.</p><p><strong>Results: </strong>We observed a reduction in GS activity and increased MAO-B content, both in 4 weeks and in 16 weeks, reinforcing the idea that astroglial dysfunction precedes the amyloid phase. These alterations were accompanied by an increase in the content of ornithine decarboxylase 1 (ODC1), which catalyzes the synthesis of putrescine (substrate for GABA synthesis, via MAO-B), and a reduction in the gene expression of arginine-glycine amidinotransferase (AGAT), an enzyme involved in the synthesis of creatine, and in the generation of GABA agonists. These changes were only seen in the amyloid phase of the AD model.</p><p><strong>Conclusions: </strong>Our findings contribute to explain the greater damage that occurs in energy metabolism at this stage, in addition to the greater GABAergic loss. The changes reinforce the importance of the STZ model and further our understanding of the changes in both AD phases.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1381-1393"},"PeriodicalIF":2.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}