Current Alzheimer research最新文献

{"title":"Distribution of Cortical Atrophy Associated with Cognitive Decline in Alzheimer's Disease: A Cross-Sectional Quantitative Structural MRI Study from PUMCH Dementia Cohort.","authors":"Chenhui Mao,&nbsp;Bo Hou,&nbsp;Jie Li,&nbsp;Shanshan Chu,&nbsp;Xinying Huang,&nbsp;Jie Wang,&nbsp;Liling Dong,&nbsp;Caiyan Liu,&nbsp;Feng Feng,&nbsp;Bin Peng,&nbsp;Jing Gao","doi":"10.2174/1567205019666220905145756","DOIUrl":"https://doi.org/10.2174/1567205019666220905145756","url":null,"abstract":"<p><strong>Background: </strong>Quantitative measures of atrophy on structural MRI are sensitive to the neurodegeneration that occurs in AD, and the topographical pattern of atrophy could serve as a sensitive and specific biomarker.</p><p><strong>Objective: </strong>We aimed to examine the distribution of cortical atrophy associated with cognitive decline and disease stage based on quantitative structural MRI analysis in a Chinese cohort to inform clinical diagnosis and follow-up of AD patients.</p><p><strong>Methods: </strong>One hundred and eleven patients who were clinically diagnosed with probable AD were enrolled. All patients completed a systemic cognitive evaluation and domain-specific batteries. The severity of cognitive decline was defined by MMSE score: 1-10 severe, 11-20 moderate, and 21-30 mild. Cortical volume and thickness determined using 3D-T1 MRI data were analyzed using voxelbased morphometry and surface-based analysis supported by the DR. Brain Platform.</p><p><strong>Results: </strong>The male:female ratio was 38:73. The average age was 70.8 ± 10.6 years. The mild: moderate: severe ratio was 48:38:25. Total grey matter volume was significantly related to cognition while the relationship between white matter volume and cognition did not reach statistical significance. The volume of the temporal-parietal-occipital cortex was most strongly associated with cognitive decline in group analysis, while the hippocampus and entorhinal area had a less significant association with cognitive decline. Volume of subcortical grey matter was also associated with cognition. Volume and thickness of temporoparietal cortexes were significantly correlated with the cognitive decline, with a left predominance observed.</p><p><strong>Conclusion: </strong>Cognitive deterioration was associated with cortical atrophy. Volume and thickness of the left temporal-parietal-occipital cortex were most important in early diagnosis and longitudinal evaluation of AD in clinical practice. Cognitively relevant cortices were left predominant.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 8","pages":"618-627"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes/Dementia in Sub-Saharian Africa and Nigerian Women in the Eye of Storm.","authors":"Efosa K Oghagbon,&nbsp;José Prieto-Pino,&nbsp;Faeren Dogoh,&nbsp;Monday Ogiator,&nbsp;Lydia Giménez-Llort","doi":"10.2174/1567205018666211116093747","DOIUrl":"https://doi.org/10.2174/1567205018666211116093747","url":null,"abstract":"<p><p>In the next few years, the prevalence of diabetes mellitus (DM) is projected to dramatically increase globally, but most of the cases will occur in low-to-middle-income countries. Some of the major risk factors for diabetes accelerate the development of dementia in African-Americans, thus leading to a higher prevalence of dementia than Caucasians. Sub-Saharian Africa women have a disproportionately two-to-eight fold increased prevalence of dementia. In the eye of this storm, Nigeria holds the highest number of diabetics on the African continent, and its prevalence is rising in parallel to obesity, hypertension, and the population's aging. The socio-economic impact of the rising prevalence of DM and dementia will be huge and unsustainable for the healthcare system in Nigeria, as has been recognized in developed economies. Here, we analyze the current situation of women's health in Nigeria and explore future perspectives and directions. The complex interplay of factors involved in diabetes and dementia in Nigerian women include key biological agents (metabolic syndrome, vascular damage, inflammation, oxidative stress, insulin resistance), nutritional habits, lifestyle, and anemia, that worsen with comorbidities. In addition, restricted resources, lack of visibility, and poor management result in a painful chain that increases the risk and burden of disease in Nigerian women from youth to old ages. Heath policies to increase the ratio of mental health professionals per number of patients, mostly in rural areas, foment of proactive primary care centers, and interventions targeting adolescents and adult women and other specific mothers-children pairs are strongly required for a sustainable development goal.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 2","pages":"161-170"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39628992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine-Based Learning Shifting to Prediction Model of Deteriorative MCI Due to Alzheimer's Disease - A Two-Year Follow-Up Investigation.","authors":"Xiaohui Zhao,&nbsp;Haijing Sui,&nbsp;Chengong Yan,&nbsp;Min Zhang,&nbsp;Haihan Song,&nbsp;Xueyuan Liu,&nbsp;Juan Yang","doi":"10.2174/1567205020666221019122049","DOIUrl":"https://doi.org/10.2174/1567205020666221019122049","url":null,"abstract":"<p><strong>Objective: </strong>The aim of the present work was to investigate the features of the elderly population aged ≥65 yrs and with deteriorative mild cognitive impairment (MCI) due to Alzheimer's disease (AD) to establish a prediction model.</p><p><strong>Methods: </strong>A total of 105 patients aged ≥65 yrs and with MCI were followed up, with a collection of 357 features, which were derived from the demographic characteristics, hematological indicators (serum Aβ1-40, Aβ1-42, P-tau and MCP-1 levels, APOE gene), and multimodal brain Magnetic Resonance Imaging (MRI) imaging indicators of 116 brain regions (ADC, FA and CBF values). Cognitive function was followed up for 2 yrs. Based on the Python platform Anaconda, 105 patients were randomly divided into a training set (70%) and a test set (30%) by analyzing all features through a random forest algorithm, and a prediction model was established for the form of rapidly deteriorating MCI.</p><p><strong>Results: </strong>Of the 105 patients enrolled, 41 deteriorated, and 64 did not come within 2 yrs. Model 1 was established based on demographic characteristics, hematological indicators and multi-modal MRI image features, the accuracy of the training set being 100%, the accuracy of the test set 64%, sensitivity 50%, specificity 67%, and AUC 0.72. Model 2 was based on the first five features (APOE4 gene, FA value of left fusiform gyrus, FA value of left inferior temporal gyrus, FA value of left parahippocampal gyrus, ADC value of right calcarine fissure as surrounding cortex), the accuracy of the training set being 100%, the accuracy of the test set 85%, sensitivity 91%, specificity 80% and AUC 0.96. Model 3 was based on the first four features of Model 1, the accuracy of the training set is 100%, the accuracy of the test set 97%, sensitivity100%, specificity 95% and AUC 0.99. Model 4 was based on the first three characteristics of Model 1, the accuracy of the training set being 100%, the accuracy of the test set 94%, sensitivity 92%, specificity 94% and AUC 0.96. Model 5 was based on the hematological characteristics, the accuracy of the training set is 100%, the accuracy of the test set 91%, sensitivity 100%, specificity 88% and AUC 0.97. The models based on the demographic characteristics, imaging characteristics FA, CBF and ADC values had lower sensitivity and specificity.</p><p><strong>Conclusion: </strong>Model 3, which has four important predictive characteristics, can predict the rapidly deteriorating MCI due to AD in the community.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 10","pages":"708-715"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10617602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 Levels in Alzheimer's: The Relation Between Neuroinflammatory Pathway and Severity of Dementia.","authors":"Nazrin Gulmammadli, Dildar Konukoğlu, Eda Merve Kurtuluş, Didem Tezen, Muhammed Ibrahim Erbay, Melda Bozluolçay","doi":"10.2174/1567205020666221226140721","DOIUrl":"10.2174/1567205020666221226140721","url":null,"abstract":"<p><p>Alzheimer's disease (AD), which affects the world's aging population, is a progressive neurodegenerative disease requiring markers or tools to accurately and easily diagnose and monitor the process.</p><p><strong>Objective: </strong>In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukin-6 (IL-6), Amyloid βeta-42 (Aβ- 42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation.</p><p><strong>Methods: </strong>Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n = 21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, and p-tau181 levels.</p><p><strong>Results: </strong>Levels of serum Aβ-42, SIRT1, HMGB1, and IL-6 were significantly higher (p< 0.001, p< 0.01, p< 0.001, and p< 0.001, respectively), and TLR4 levels were significantly lower (p< 0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels.</p><p><strong>Conclusion: </strong>Our results show that the levels of the Aβ42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"841-848"},"PeriodicalIF":1.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10445315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Inflammatory Cytokines in the Conversion of Mild Cognitive Impairment to Dementia: A Prospective Study.","authors":"Raúl Romero-Sevilla,&nbsp;Fidel López-Espuela,&nbsp;José Manuel Fuentes,&nbsp;Beatriz Duque de San Juan,&nbsp;Juan Carlos Portilla-Cuenca,&nbsp;Carmen Cámara Hijon,&nbsp;Ignacio Casado-Naranjo","doi":"10.2174/1567205019666220127102640","DOIUrl":"https://doi.org/10.2174/1567205019666220127102640","url":null,"abstract":"<p><strong>Background: </strong>The effect that cytokines can exert on the progression from mild cognitive impairment (MCI) to ongoing dementia is a matter of debate and the results obtained so far are controversial.</p><p><strong>Objective: </strong>The aim of the study is to analyze the influence of markers of subclinical inflammation on the progression of MCI to dementia.</p><p><strong>Methods: </strong>A prospective study involving a cohort of patients ≥ 65 years of age diagnosed with MCI and followed for 3 years was conducted. 105 patients were enrolled, and serum concentrations of several subclinical inflammatory markers were determined.</p><p><strong>Results: </strong>After 3.09 (2 - 3.79) years of follow-up, 47 (44.76%) patients progressed to dementia. Alpha 1-antichymotrypsin (ACT) was found to be significantly higher in patients who progressed to dementia (486.45 ± 169.18 vs. 400.91 ± 163.03; p = 0.012), and observed to significantly increase the risk of developing dementia in patients with mild cognitive impairment (1.004, 1.001-1.007; p = 0.007). IL-10 levels were significantly higher in those who remained stable (6.69 ± 18.1 vs. 32.54 ± 89.6; p = 0.04). Regarding the type of dementia to which our patients progressed, we found that patients who developed mixed dementia had higher IL-4 levels than those who converted to AD (31.54 ± 63.6 vs. 4.43 ± 12.9; p = 0.03). No significant differences were observed between the groups with regard to the ESR and LPa, CRP, IL-1 and TNF-α levels.</p><p><strong>Conclusion: </strong>ACT levels have a significant predictive value in the conversion of MCI to dementia. IL-10 levels could be a protective factor. It is necessary to conduct studies with serial determinations of these and other inflammatory markers in order to determine their effect on the progression of MCI to dementia.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"68-75"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39727261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation in the CNS: Understanding Various Aspects of the Pathogenesis of Alzheimer's Disease.","authors":"Julia Doroszkiewicz,&nbsp;Piotr Mroczko,&nbsp;Agnieszka Kulczyńska-Przybik","doi":"10.2174/1567205018666211202143935","DOIUrl":"https://doi.org/10.2174/1567205018666211202143935","url":null,"abstract":"<p><p>Alzheimer's disease is a progressive and deadly neurodegenerative disorder and one of the most common causes of dementia globally. Current, insufficiently sensitive and specific methods of early diagnosing and monitoring this disease prompt a search for new tools. Numerous literature data have indicated that the pathogenesis of Alzheimer's disease (AD) is not limited to the neuronal compartment but involves various immunological mechanisms. Neuroinflammation has been recognized as a very important process in AD pathology. It seems to play pleiotropic roles, both neuroprotective and neurodegenerative, in the development of cognitive impairment depending on the stage of the disease. Mounting evidence demonstrates that inflammatory proteins could be considered biomarkers of disease progression. Therefore, the present review summarizes the role of some inflammatory molecules and their potential utility in detecting and monitoring dementia severity. This paper also provides a valuable insight into new mechanisms leading to the development of dementia, which might be useful in discovering possible anti-inflammatory treatment.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"16-31"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/84/CAR-19-16.PMC9127729.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39775259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte Reactivity in Alzheimer's Disease: Therapeutic Opportunities to Promote Repair.","authors":"Nazanin Mirzaei,&nbsp;Nicola Davis,&nbsp;Tsz Wing Chau,&nbsp;Magdalena Sastre","doi":"10.2174/1567205018666211029164106","DOIUrl":"https://doi.org/10.2174/1567205018666211029164106","url":null,"abstract":"<p><p>Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer's Disease (AD), with the prominent presence of reactive astrocytes surrounding amyloid-β plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demonstrated that astrocytes from AD brains are different from \"normal\" healthy astrocytes, showing dysregulations in areas such as neurotransmitter recycling, including glutamate and GABA, and impaired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology, worsening of the inflammatory profile, and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal models has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"1-15"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39666062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Intensity Electromagnetic Fields Act via Voltage-Gated Calcium Channel (VGCC) Activation to Cause Very Early Onset Alzheimer's Disease: 18 Distinct Types of Evidence.","authors":"Martin L Pall","doi":"10.2174/1567205019666220202114510","DOIUrl":"https://doi.org/10.2174/1567205019666220202114510","url":null,"abstract":"<p><p>Electronically generated electromagnetic fields (EMFs), including those used in wireless communication such as cell phones, Wi-Fi and smart meters, are coherent, producing very high electric and magnetic forces, which act on the voltage sensor of voltage-gated calcium channels to produce increases in intracellular calcium [Ca²⁺]i. The calcium hypothesis of Alzheimer's disease (AD) has shown that each of the important AD-specific and nonspecific causal elements is produced by excessive [Ca²⁺]i. [Ca²⁺]i acts in AD via excessive calcium signaling and the peroxynitrite/oxidative stress/inflammation pathway, which are each elevated by EMFs.An apparent vicious cycle in AD involves amyloid-beta protein (Aβ) and [Ca²⁺]i. Three types of epidemiology suggest EMF causation of AD, including early onset AD. Extensive animal model studies show that low intensity EMFs cause neurodegeneration, including AD, with AD animals having elevated levels of Aβ, amyloid precursor protein and BACE1. Rats exposed to pulsed EMFs every day are reported to develop universal or near universal very early onset neurodegeneration, including AD; these findings are superficially similar to humans with digital dementia. EMFs producing modest increases in [Ca²⁺]i can also produce protective, therapeutic effects. The therapeutic pathway and peroxynitrite pathway inhibit each other. A summary of 18 different findings is provided, which collectively provide powerful evidence for EMF causation of AD. The author is concerned that smarter, more highly pulsed \"smart\" wireless communication may cause widespread very, very early onset AD in human populations.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 2","pages":"119-132"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2a/c9/CAR-19-119.PMC9189734.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kappa/Lambda light-chain typing in Alzheimer's Disease.","authors":"Zelal Zuhal Kaya,&nbsp;Mete Bora Tuzuner,&nbsp;Betul Sahin,&nbsp;Emel Akgun,&nbsp;Fehime Aksungar,&nbsp;Sebile Koca,&nbsp;Muhittin Serdar,&nbsp;Sevki Sahin,&nbsp;Nilgun Cinar,&nbsp;Sibel Karsidag,&nbsp;Hasmet Ayhan Hanagasi,&nbsp;Meltem Kilercik,&nbsp;Mustafa Serteser,&nbsp;Ahmet Tari K Baykal","doi":"10.2174/1567205019666220131101334","DOIUrl":"https://doi.org/10.2174/1567205019666220131101334","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. The diagnosis of Alzheimer's disease according to symptomatic events is still a puzzling task. Developing a biomarker-based, low-cost, and high-throughput test, readily applicable in clinical laboratories, dramatically impacts the rapid and reliable detection of the disease.</p><p><strong>Objective: </strong>This study aimed to develop an accurate, sensitive, and reliable screening tool for diagnosing Alzheimer's disease, which can significantly reduce the cost and time of existing methods.</p><p><strong>Methods: </strong>We have employed a MALDI-TOF-MS-based methodology combined with a microaffinity chromatography enrichment approach using affinity capture resins to determine serum kappa (κ) and lambda (λ) light chain levels in control and patients with AD.</p><p><strong>Results: </strong>We observed a statistically significant difference in the kappa light chain over lambda light chain (κLC/λLC) ratios between patients with AD and controls (mean difference -0,409; % 95 CI:- 0.547 to -0.269; p<0.001). Our method demonstrated higher sensitivity (100.00%) and specificity (71.43%) for discrimination between AD and controls.</p><p><strong>Conclusion: </strong>We have developed a high-throughput screening test with a novel sample enrichment method for determining κLC/λLC ratios associated with AD diagnosis. Following further validation, we believe our test has the potential for clinical laboratories.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"84-93"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39752864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA Hypomethylation and Unchanged DNA Methylation Levels in the Cortex of ApoE4 Carriers and Alzheimer's Disease Subjects.","authors":"Wei-Bin Shen,&nbsp;James Jiao Yang,&nbsp;Peixin Yang","doi":"10.2174/1567205019666220831125142","DOIUrl":"https://doi.org/10.2174/1567205019666220831125142","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and ApoE4 variants are significant risk factors for AD. Epigenetic modifications are involved in AD pathology. However, it is unclear whether DNA/RNA methylation plays a role in AD pathology, and dysregulation of DNA/RNA methylation occurs in ApoE4 carriers.</p><p><strong>Objective: </strong>The present study aimed to determine whether dysregulation of DNA/RNA methylation is present in the brains of ApoE4 carriers and AD patients.</p><p><strong>Methods: </strong>In this study, postmortem brain tissues from carriers of ApoE4 and ApoE3, from AD and non- AD controls, were used in the analysis of DNA/RNA methylation, methyltransferases, and their demethylases.</p><p><strong>Results: </strong>Immunofluorescence staining indicates that RNA methylation is suppressed in ApoE4 carriers. Further analysis shows that the expression of RNA methyltransferases and an RNA methylation reader is suppressed in ApoE4 carriers, whereas RNA demethylase expression is increased. RNA hypomethylation occurs in NeuN+ neurons in ApoE4 carriers and AD patients. Furthermore, in ApoE4 carriers, both DNA methyltransferases and demethylases are downregulated, and overall DNA methylation levels are unchanged.</p><p><strong>Conclusion: </strong>Our finding indicates that RNA methylation decreased in ApoE4 carriers before AD pathology and AD individuals. The expression of RNA methyltransferases and RNA methylation reader is inhibited, and RNA demethylase is upregulated in ApoE4 carriers, which leads to suppression of RNA methylation, and the suppression precedes the AD pathogenesis and persists through AD pathology.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 7","pages":"530-540"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10613223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}