Journal of Alzheimer's Disease最新文献

Longitudinal and concurrent C-reactive protein and diet associations with cognitive function in the population-based Tromsø study.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-02-02 DOI: 10.1177/13872877251317624

Olena Iakunchykova, Henrik Schirmer, James M Roe, Øystein Sørensen, Tom Wilsgaard, Laila A Hopstock, Anne Elise Eggen, Michael E Benros, Chi-Hua Chen, Yunpeng Wang

{"title":"Longitudinal and concurrent C-reactive protein and diet associations with cognitive function in the population-based Tromsø study.","authors":"Olena Iakunchykova, Henrik Schirmer, James M Roe, Øystein Sørensen, Tom Wilsgaard, Laila A Hopstock, Anne Elise Eggen, Michael E Benros, Chi-Hua Chen, Yunpeng Wang","doi":"10.1177/13872877251317624","DOIUrl":"https://doi.org/10.1177/13872877251317624","url":null,"abstract":"Background: Immune dysregulation has been implicated in Alzheimer's disease; however, precise mechanisms and timing have not been established.Objective: To investigate the concurrent and longitudinal associations of serum C-reactive protein (CRP) and dietary inflammatory index (DII) with cognitive decline as observed in Alzheimer's disease.Methods: The study was based on 7613 individuals who participated in Tromsø6 (2007-2008) and Tromsø7 (2015-2016). We analyzed the relationship between CRP levels, DII, and cognitive function cross-sectionally using linear regression. We used mediation analysis to examine if CRP mediates the effects of DII on cognitive function. Further, we related baseline serum CRP to cognitive function and to change in cognitive function after 7 years of follow up. We used linear mixed models to relate changes in CRP levels to changes in cognitive function measured at two time points with 7 years apart.Results: Both CRP level and DII were cross-sectionally inversely associated with cognitive function (psychomotor speed, executive function). There was no prospective relationship between CRP level at baseline and cognitive function after 7 years of follow up. Increase in CRP levels was associated with decrease in cognitive function (psychomotor speed, executive function, and verbal memory) observed between two measurements 7 years apart. The mediation model did not show convincing evidence of a mediating effect of CRP in the association between diet and cognitive function.Conclusions: After comprehensive analysis of associations between CRP, DII and cognitive function, we conclude that CRP is likely to reflect the changes in inflammatory environment occurring in parallel with cognitive decline.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251317624"},"PeriodicalIF":3.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080054","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

Microglial polarization in Alzheimer's disease: Mechanisms, implications, and therapeutic opportunities.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-02-02 DOI: 10.1177/13872877241313223

Xinmao Yang, Jie Wang, Xiaotao Jia, Yaqian Yang, Yan Fang, Xiaoping Ying, Hong Li, Meiqian Zhang, Jing Wei, Yanfang Pan

引用次数: 0

Iron chelation by oral deferoxamine treatment decreased brain iron and iron signaling proteins.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-02-02 DOI: 10.1177/13872877241313031

Max A Thorwald, Naomi S Sta Maria, Ararat Chakhoyan, Peggy A O'Day, Russell E Jacobs, Berislav Zlokovic, Caleb E Finch

{"title":"Iron chelation by oral deferoxamine treatment decreased brain iron and iron signaling proteins.","authors":"Max A Thorwald, Naomi S Sta Maria, Ararat Chakhoyan, Peggy A O'Day, Russell E Jacobs, Berislav Zlokovic, Caleb E Finch","doi":"10.1177/13872877241313031","DOIUrl":"https://doi.org/10.1177/13872877241313031","url":null,"abstract":"Background: Deferoxamine (DFO) and other iron chelators are clinically used for cancer and stroke. They may also be useful for Alzheimer's disease (AD) to diminish iron from microbleeds. DFO may also stimulate antioxidant membrane repair which is impaired during AD. DFO and other chelators do enter the brain despite some contrary reports.Objective: Low dose, oral DFO was given in lab chow to wildtype (WT) C57BL/6 mice to evaluate potential impact on iron levels, iron-signaling and storage proteins, and amyloid-β protein precursor (AβPP) and processing enzymes. Young WT mice do not have microbleeds or disrupted blood-brain barrier of AD mice.Methods: Iron was measured by MRI and chemically after two weeks of dietary DFO. Cerebral cortex was examined for changes in iron metabolism, antioxidant signaling, and AβPP processing by western blot.Results: DFO decreased brain iron 18% (p < 0.01) estimated by R2 MRI and decreased seven major proteins that mediate iron metabolism by at least 25%. The iron storage proteins ferritin light and heavy chain decreased by at least 30%. AβPP and secretase enzymes also decreased by 30%.Conclusions: WT mice respond to DFO with decreased AβPP, amyloid processing enzymes, and antioxidant repair. Potential DFO treatment for early-stage AD by DFO should consider the benefits of lowered AβPP and secretase enzymes.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877241313031"},"PeriodicalIF":3.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080053","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

MicroRNA-based recent research developments in Alzheimer's disease.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-02-02 DOI: 10.1177/13872877241313397

Jaime Ramirez-Gomez, Sarthak Dalal, Davin Devara, Bhupender Sharma, Daniela Rodarte, Subodh Kumar

{"title":"MicroRNA-based recent research developments in Alzheimer's disease.","authors":"Jaime Ramirez-Gomez, Sarthak Dalal, Davin Devara, Bhupender Sharma, Daniela Rodarte, Subodh Kumar","doi":"10.1177/13872877241313397","DOIUrl":"https://doi.org/10.1177/13872877241313397","url":null,"abstract":"Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by memory and physical impairment in aged individuals. microRNAs (miRNAs) are small, single-stranded noncoding RNAs that induce translational repression by binding to the 3' UTR of a target mRNA. miRNAs play a crucial role in neurological activity by mediating cellular proliferation, synaptic plasticity, apoptosis and more. Ongoing research in patents and clinical trials have called attention to promising miRNAs as biomarkers and therapeutics in AD. Recent research has shown that miRNAs are aberrantly expressed in AD brain, blood, cerebrospinal fluid and serum. Attenuated miRNA expressions have diagnostic potential in AD by interacting with amyloid-β synthesis, phosphorylated tau, and neurofibrillary tangles. In this study, miRNA-29a, miRNA-125b, miRNA-34a, miRNA-146a, and miRNA-155 have shown promise as potential biomarker candidates for AD. Improving cognitive symptoms can be traced to restoring the endogenous miRNA activity by synthesizing miRNA mimics and miRNA antisense oligonucleotides. miRNA-483-5p, miRNA-188-5p, miRNA-219, miRNA135a/5p, miRNA-23/23b-3p, miRNA-124, and miRNA-455-3p are growing therapeutics for AD. However, miRNA-based therapeutics struggle outside of preclinical testing. miRNA-107, miRNA-206, miRNA-30/7, and miRNA-142-3p face bottlenecks in clinical trials due to a lack of experimental design, transparency and volunteer size. Patenting recent miRNA-based developments demonstrates the commitment in identifying a new biomarker and/or therapeutic for AD.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877241313397"},"PeriodicalIF":3.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080056","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

Unveiling the link between APOE ε4, environmental factors, and Alzheimer's disease in North Lebanon: A case-control study.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-02-02 DOI: 10.1177/13872877241307307

Mohamed Khaled, Hadi Al-Jamal, Dana Matar, Antonia Ibrahim, Layla Tajer, Nicole Issa, Reem El-Mir, Joudi Hantour

{"title":"Unveiling the link between APOE ε4, environmental factors, and Alzheimer's disease in North Lebanon: A case-control study.","authors":"Mohamed Khaled, Hadi Al-Jamal, Dana Matar, Antonia Ibrahim, Layla Tajer, Nicole Issa, Reem El-Mir, Joudi Hantour","doi":"10.1177/13872877241307307","DOIUrl":"https://doi.org/10.1177/13872877241307307","url":null,"abstract":"Background: Alzheimer's disease (AD) is a multifactorial and progressive neurodegenerative disorder influenced by a variety of genetic and environmental factors. The apolipoprotein E (APOE) gene is known to have a pivotal impact on disease onset, yet clinical studies on its impact on AD remain scarce in Lebanon.Objective: This study investigates the interplay between environmental risk factors, the APOE gene, and AD in North Lebanon.Methods: A case-control study was conducted with 136 individuals, including 57 AD patients and 79 normal individuals, among which 55 individuals were verified to be cognitively normal via the Mini-Mental State Examination (MMSE). A comprehensive survey was used to collect data on lifestyle factors, medical history, and other possible diseases and deficiencies. Blood samples were collected from all participants, then their DNA was isolated and stored. Real-time PCR was adopted for genotyping.Results: The total APOE ε4 allele prevalence was reduced from 19.1% to 16.1% after MMSE adjustment. Based on the univariate analysis, factors like age, illiteracy, vitamin and iron deficiencies, blood pressure, and chronic diseases were identified as prominent risk factors, while the allele showed no significant correlation with AD. However, in the multivariable analysis, this allele emerged as a key risk factor (p = 0.04). Factors like age ≥ 65, vitamin deficiency, iron deficiency, blood pressure, and other chronic diseases were consistently significant.Conclusions: Our results provide significant evidence that the influence of APOE ε4 on AD is governed by several environmental factors such as age, vitamin and iron deficiencies, high blood pressure, and chronic diseases.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877241307307"},"PeriodicalIF":3.4,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080059","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

Immune cells: Mediators in the metabolites and Alzheimer's disease.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-01-29 DOI: 10.1177/13872877241313140

Erdong Zhang, Fengqiu Dai, Ling Tao, Yanqin Chen, Tingting Chen, Xiangchun Shen

{"title":"Immune cells: Mediators in the metabolites and Alzheimer's disease.","authors":"Erdong Zhang, Fengqiu Dai, Ling Tao, Yanqin Chen, Tingting Chen, Xiangchun Shen","doi":"10.1177/13872877241313140","DOIUrl":"https://doi.org/10.1177/13872877241313140","url":null,"abstract":"Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that predominantly affects elderly individuals across the globe. While genetic, environmental, and lifestyle factors are known to influence the onset of AD, the underlying mechanisms remain unclear.Objective: To elucidate the intricate interplay between metabolites and immune cell activation in the ethology of AD, and to determine their collective impact on AD risk.Methods: We conducted a comprehensive analysis of genome-wide association studies data to examine the relationships between metabolites, immune cell phenotypes, and the risk of AD. Our study encompassed a comprehensive examination involving 731 distinct immune cell types, 1400 metabolites, and a large cohort comprising10,520 AD cases with 401,661 controls. We employed univariate Mendelian randomization to assess bidirectional relationships between metabolites and AD, metabolites and immune cells, as well as immune cells and AD. Subsequently, multivariate Mendelian randomization was then applied to evaluate the potential mediating role of immune cells on the relationship between metabolites and AD.Results: Specific metabolites, the histidine/pyruvate ratio and homoarginine, were positively associated with the risk of AD, mediated by immune cells. Conversely, 4-hydroxycoumarin and glycolithocholate sulfate showed protective associations against AD. Immune cell markers, CD64 on monocytes and HLA DR on CD14+ CD16- monocytes were linked to higher AD risk, while CD33dim HLA DR+ CD11b- myeloid cells and HLA DR on CD8+ T cells were protective.Conclusions: This study highlights the critical role of immune cells in the pathogenesis of AD, demonstrating how their interaction with specific metabolites influences disease risk.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877241313140"},"PeriodicalIF":3.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059141","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

Corrigendum to "Diabetic Retinopathy and Brain Structure, Cognition Function, and Dementia: A Bidirectional Mendelian Randomization Study".

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-01-29 DOI: 10.1177/13872877241308424

引用次数: 0

The use of outpatient support services: Differences between people with mild cognitive impairment and people with mild to moderate dementia.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-01-28 DOI: 10.1177/13872877251314060

Anne Keefer, Nikolas Dietzel, Peter L Kolominsky-Rabas, Elmar Graessel

{"title":"The use of outpatient support services: Differences between people with mild cognitive impairment and people with mild to moderate dementia.","authors":"Anne Keefer, Nikolas Dietzel, Peter L Kolominsky-Rabas, Elmar Graessel","doi":"10.1177/13872877251314060","DOIUrl":"https://doi.org/10.1177/13872877251314060","url":null,"abstract":"Background: Little is known about the utilization of outpatient support services by people with mild cognitive impairment (MCI).Objective: This study aimed to analyze the use of support services by people with MCI compared to people with mild to moderate dementia.Methods: The data basis is the multicenter, prospective register study 'Digital Dementia Register Bavaria - digiDEM Bayern'. The sample consists of 913 people with cognitive impairment, including 389 with MCI and 524 with mild to moderate dementia. Classification into 'MCI' and 'mild to moderate dementia' is based on the Mini-Mental State Examination and Montreal Cognitive Assessment. The use of support services was surveyed using the Dementia Assessment of Service Needs. Fisher's exact test and multiple linear regression were conducted to analyze for group differences.Results: Four out of thirteen support services are used less frequently by people with MCI than by people with mild to moderate dementia: 'Outpatient care' (p < 0.001, φ = -0.199), 'Acquisition of aids' (p = 0.004, φ = -0.096), 'Adult daycare' (p < 0.001, φ = -0.290), and 'Respite care' (p = 0.029, φ = -0.095). Even the overall utilization rate is lower for people with MCI (b = -0.18, p = 0.027), although other factors such as a care level (b = 1.01, p < 0.001) are more strongly related.Conclusions: There are differences in utilization between people with MCI and people with mild to moderate dementia, but these are small. Therefore, access to support services should be provided at the first signs of cognitive impairment.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251314060"},"PeriodicalIF":3.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052390","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

Di Huang Yi Zhi Fang improves cognitive function in APP/PS1 mice by inducing neuronal mitochondrial autophagy through the PINK1-parkin pathway.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-01-28 DOI: 10.1177/13872877241299832

Limin Zhang, Hongmei An, Rongrong Zhen, Tong Zhang, Minrui Ding, Mengxue Zhang, Yiguo Sun, Chao Gu

{"title":"Di Huang Yi Zhi Fang improves cognitive function in APP/PS1 mice by inducing neuronal mitochondrial autophagy through the PINK1-parkin pathway.","authors":"Limin Zhang, Hongmei An, Rongrong Zhen, Tong Zhang, Minrui Ding, Mengxue Zhang, Yiguo Sun, Chao Gu","doi":"10.1177/13872877241299832","DOIUrl":"https://doi.org/10.1177/13872877241299832","url":null,"abstract":"Background: Alzheimer's disease (AD) is an irreversible age-related neurodegenerative condition characterized by the deposition of amyloid-β (Aβ) peptides and neurofibrillary tangles. Di Huang Yi Zhi (DHYZ) formula, a traditional Chinese herbal compound comprising several prescriptions, demonstrates properties that improve cognitive abilities in clinical. Nonetheless, its molecular mechanisms on treating AD through improving neuron cells mitochondria function have not been deeply investigated.Objective: This study administered DHYZ to APP/PS1 mice to explore its potential therapeutic mechanisms in AD treatment.Methods: APP/PS1 transgenic mice were given DHYZ (L, M, H), donepezil, or distilled water for a consecutive 12-week period. The Morris water maze test was used to assess memory capacity, transmission electron microscopy was used to observe mitochondrial and synaptic structures, immunohistochemistry and western blot detected proteins involved in the mitochondrial autophagy pathway, ELISA measured serum Aβ content, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assessed neuronal cell apoptosis.Results: DHYZ demonstrates a notable therapeutic impact on mice with AD, effectively improving cognitive and memory impairments. DHYZ decreases Aβ accumulation in the hippocampus by reducing BACE1 activity and enhancing Aβ clearance through the blood-brain barrier. Additionally, DHYZ significantly suppresses neuronal apoptosis, enhances synaptic structure, and increases synapse numbers, processes strongly linked to the activation of mitochondrial PINK1-Parkin autophagy.Conclusions: DHYZ enhances cognitive function in APP/PS1 mice by stimulating neuronal mitochondrial autophagy through the PINK1-Parkin pathway.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877241299832"},"PeriodicalIF":3.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052389","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

Dancing towards speech improvement: Repurposing dance for motor speech deficits in neurodegenerative diseases.

IF 3.4 3区医学

Journal of Alzheimer's Disease Pub Date : 2025-01-27 DOI: 10.1177/13872877241313304

Constantina Theofanopoulou

{"title":"Dancing towards speech improvement: Repurposing dance for motor speech deficits in neurodegenerative diseases.","authors":"Constantina Theofanopoulou","doi":"10.1177/13872877241313304","DOIUrl":"https://doi.org/10.1177/13872877241313304","url":null,"abstract":"Dance or rhythmic movement-based training has demonstrated significant efficacy in addressing a range of motor and cognitive deficits associated with neurodegenerative diseases like Parkinson's and Alzheimer's diseases. Leveraging both human and non-human animal behavioral and neurobiological evidence, I hypothesize a possible untapped role of dance training in mitigating impairments in the motor control of speech, a complex sensorimotor behavior affected in these conditions. Here, this hypothesis is supported by an in-depth examination of motor speech deficits in Parkinson's and Alzheimer's diseases, at a behavioral, physiological, and neural level. Additionally, literature on the impact of dance training on behaviors and brain pathways possibly relevant to speech motor control in populations with neurodegenerative diseases is thoroughly reviewed. Synthesizing these findings, I propose repurposing dance as a novel treatment for motor speech deficits and outline specific experiments to test this hypothesis. By comprehensively investigating the full spectrum of the effects of a motor-based training, i.e., dance, on often overlooked motor-based behaviors, such as speech, we may uncover novel therapeutic avenues of a practice that has already shown promising implications.","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877241313304"},"PeriodicalIF":3.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046583","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