Current Alzheimer research最新文献

{"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}

{"title":"Complex Processes Underlying the Dynamic Changes of D-serine Levels in AD Brains.","authors":"Xiance Ni,&nbsp;Hisashi Mori","doi":"10.2174/1567205019666220328123048","DOIUrl":"https://doi.org/10.2174/1567205019666220328123048","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular β-amyloid (Aβ) plaques and cognitive impairments. D-Serine, produced by the enzyme serine racemase (SR) in the brain, functions as an endogenous co-agonist at the glycine-binding site of N-methyl-D-aspartate receptor (NMDAR), has been implicated in the pathophysiological progression of AD.</p><p><strong>Objectives: </strong>Evidence regarding the understanding of the role and dynamic modulation of D-serine during AD progression remains controversial. This literature review aims to offer novel research directions for studying the functions and metabolisms of D-serine in AD brains.</p><p><strong>Methods: </strong>We searched PubMed, using D-serine/SR and AD as keywords. Studies related to NMDAR dysfunction, neuronal excitotoxicity, D-serine dynamic changes and inflammatory response were included.</p><p><strong>Results: </strong>This review primarily discusses: (i) Aβ oligomers' role in NMDAR dysregulation, and the subsequent synaptic dysfunction and neuronal damage in AD, (ii) D-serine's role in NMDAR-elicited excitotoxicity, and (iii) the involvement of D-serine and SR in AD-related inflammatory pathological progression.</p><p><strong>Conclusion: </strong>We also presented supposed metabolism and dynamic changes of D-serine during AD progression and hypothesized that: (i) the possible modulation of D-serine levels or SR expression as an effective method of alleviating neurotoxicity during AD pathophysiological progression, and (ii) the dynamic changes of D-serine levels in AD brains possibly resulting from complex processes.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 7","pages":"485-493"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10616152","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":"Primary Sjögren's Syndrome Presenting with Rapidly Progressive Dementia: A Case Report.","authors":"Konstantinos Notas,&nbsp;Vasileios Papaliagkas,&nbsp;Martha Spilioti,&nbsp;Ioannis Papagiannis,&nbsp;Petros Nemtsas,&nbsp;Athanasios Poulopoulos,&nbsp;Konstantinos Kouskouras,&nbsp;Ioannis Diakogiannis,&nbsp;Vasilios K Kimiskidis","doi":"10.2174/1567205019666220627094707","DOIUrl":"https://doi.org/10.2174/1567205019666220627094707","url":null,"abstract":"<p><strong>Background: </strong>Rapidly progressive dementias (RPDs) are dementias that progress subacutely over a time period of weeks to months. Primary Sjögren's syndrome (pSS) is an autoimmune disease that can affect any organ system and may present with a wide range of clinical features that may mimic a plethora of medical conditions and, in rare cases, may manifest as RPD. We describe a unique case of pSS, in which rapidly progressive dementia (RPD) was the first disease manifestation, and the patient's radiological and electroencephalogram findings were compatible with Creutzfeldt- Jakob disease (CJD).</p><p><strong>Case presentation: </strong>Here, we report a 58-year-old woman who presented with cognitive impairment rapidly deteriorating over the last 6 months prior to admission. Brain MRI and EEG were indicative of CJD. However, CSF 14-3-3 and tau/phospho tau ratio were within normal limits and therefore alternative diagnoses were considered. Blood tests were significant for positive antinuclear antibodies, anti-ENA, and anti-SSA and a lip biopsy was consistent with pSS. The patient was started on intravenous steroids followed by oral prednisone taper, which prevented further deterioration.</p><p><strong>Conclusion: </strong>This rare case expands the spectrum of neurological manifestations in pSS and highlights the importance of considering pSS in the differential diagnosis of RPDs in order to avoid misdiagnosis and provide appropriate treatment in a timely fashion.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"479-484"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40405424","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":"Functional Connectivity, Physical Activity, and Neurocognitive Performances in Patients with Vascular Cognitive Impairment, No Dementia.","authors":"Ya-Ting Chang,&nbsp;Chun-Ting Liu,&nbsp;Shih-Wei Hsu,&nbsp;Chen-Chang Lee,&nbsp;Pei-Ching Huang","doi":"10.2174/1567205019666220127103852","DOIUrl":"https://doi.org/10.2174/1567205019666220127103852","url":null,"abstract":"<p><strong>Background: </strong>Vascular Cognitive Impairment, No Dementia (VCIND) is a key stage at which early intervention will delay or prevent dementia. The pathophysiology of VCIND posits that a lesion in a single location in the brain has the ability to disrupt brain networks, and the subsequent abnormal Functional Connectivity (FC) of brain networks leads to deficits in corresponding neurobehavioral domains. In this study, we tested the hypothesis that disrupted anterior cingulate cortex and striatal networks mediated the effects of Physical Activity (PA) on neurobehavioral function.</p><p><strong>Methods: </strong>In 27 patients with VCIND, FC within the brain networks and neurobehavioral dysfunction were assessed. The relationship between the cognitive scores, FC, and PA was studied. The Fitbit Charge 2 was used to measure step counts, distance, and calories burned. In patients with VCIND, a cross-sectional Spearman's correlation to analyze the relationship among patient-level measures of PA, cognitive function scores, and FC strength within the brain networks.</p><p><strong>Results: </strong>Average step counts and average distance were associated with Trail Making Test B (TMB) time to completion (seconds) and Instrumental Activities of Daily Living (IADL) score (P < 0.05). The average calories burned were associated with IADL score (P = 0.009). The FC within the brain networks anchored by left caudal Anterior Cingulate Cortex (ACC) seeds (x= -5, y= 0, z= 36) and (x= -5, y= -10, z= 47) were positively correlated with average step counts and average distance, were negatively correlated with TMB time to completion (seconds), and were positively correlated with IADL score (P < 0.05). The FC within the brain networks anchored by left subgenual ACC seed (x= -5, y= 25, z= -10) were negatively correlated with average step counts and average distance were positively correlated with TMB time to completion (seconds), and were negatively correlated with IADL score (P < 0.05). The FC within the striatal networks was positively correlated with average calories burned and IADL score (P < 0.05).</p><p><strong>Conclusion: </strong>FC within the brain networks anchored by caudal ACC seeds was positively correlated with more average step counts/average distance and better IADL score; negatively correlated with longer TMB time to completion (seconds), whereas FC of subgenual ACC seed was negatively correlated with the same parameters. FC within the brain networks anchored by putamen rather than caudate or pallidum was positively correlated with average calories burned and IADL score.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"56-67"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39727262","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":"Neurodegeneration and Glial Activation Related CSF Biomarker as the Diagnosis of Alzheimer's Disease: A Systematic Review and an Updated Meta- analysis.","authors":"Yuehan Hao,&nbsp;Xu Liu,&nbsp;Ruixia Zhu","doi":"10.2174/1567205018666211208142702","DOIUrl":"https://doi.org/10.2174/1567205018666211208142702","url":null,"abstract":"<p><strong>Objective: </strong>Recently, neuron specific enolase (NSE), Visinin-like protein-1 (VLP-1), neurogranin (Ng), and YKL-40 have been identified as candidates for neuronal degeneration and glial activation biomarkers. Therefore, we perform a comprehensive meta-analysis to assess the diagnostic value of CSF NSE, VLP-1, Ng and YKL-40 in Alzheimer's disease (AD).</p><p><strong>Methods: </strong>We searched Pubmed, MEDLINE, EMBASE databases for research about the levels of CSF NSE, VLP-1, Ng and YKL-40 in AD patients compared with controls or other dementia diseases until Dec 2020.</p><p><strong>Results: </strong>The present meta-analysis contained a total of 51 studies comprising 6248 patients with dementia disorders and 3861 controls. Among them, there were 3262 patients with AD, 2456 patients with mild cognitive impairment (MCI), 173 patients with vascular dementia (VaD), 221 patients with frontotemporal dementia (FTD), and 136 with Lewy bodies dementia (DLB). Our study demonstrated that CSF NSE, VLP-1, Ng and YKL-40 levels were increased in AD as compared to healthy controls. We also observed that the CSF NSE level was higher in AD than VaD, suggesting CSF NSE might act as a key role in distinguishing between AD and VaD. Interestingly, there was a higher VLP-1 expression in AD, and a lower expression in DLB patients. Moreover, we found the CSF Ng level was increased in AD than MCI, implying CSF Ng might be a biomarker for identifying the progression of AD. Additionally, a significantly higher CSF YKL-40 level was detected not only in AD, but also in FTD, DLB, VaD, signifying YKL-40 was not sensitive in the diagnosis of AD.</p><p><strong>Conclusion: </strong>Our study confirmed that CSF levels of NSE, VLP-1, and Ng could be valuable biomarkers for identifying patients who are more susceptible to AD and distinguishing AD from other neurodegenerative dementia disorders.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"32-46"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39816129","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":"Vascular Lesions and Brain Atrophy in Alzheimer's, Vascular and Mixed Dementia: An Optimized 3T MRI Protocol Reveals Distinctive Radiological Profiles.","authors":"Matteo Cotta Ramusino,&nbsp;Paolo Vitali,&nbsp;Nicoletta Anzalone,&nbsp;Luca Melazzini,&nbsp;Francesca Paola Lombardo,&nbsp;Lisa Maria Farina,&nbsp;Sara Bernini,&nbsp;Alfredo Costa","doi":"10.2174/1567205019666220620112831","DOIUrl":"https://doi.org/10.2174/1567205019666220620112831","url":null,"abstract":"<p><strong>Background: </strong>Vascular lesions may be a common finding also in Alzheimer's dementia, but their role on cognitive status is uncertain.</p><p><strong>Objective: </strong>The study aims to investigate their distribution in patients with Alzheimer's, vascular or mixed dementia and detect any distinctive neuroradiological profiles.</p><p><strong>Methods: </strong>Seventy-six subjects received a diagnosis of Alzheimer's (AD=32), vascular (VD=26) and mixed (MD=18) dementia. Three independent raters assessed the brain images acquired with an optimized 3T MRI protocol (including (3D FLAIR, T1, SWI, and 2D coronal T2 sequences) using semiquantitative scales for vascular lesions (periventricular lesions (PVL), deep white matter lesions (DWML), deep grey matter lesions (DGML), enlarged perivascular spaces (PVS), and microbleeds (MB)) and brain atrophy (medial temporal atrophy (MTA), posterior atrophy (PA), global cortical atrophy- frontal (GCA-F) and Evans' index).</p><p><strong>Results: </strong>Raters reached a good-to-excellent agreement for all scales (ICC ranging from 0.78-0.96). A greater number of PVL (p<0.001), DWML (p<0.001), DGML (p=0.010), and PVS (p=0.001) was observed in VD compared to AD, while MD showed a significant greater number of PVL (p=0.001), DWML (p=0.002), DGML (p=0.018), and deep and juxtacortical MB (p=0.006 and p<0.001, respectively). Comparing VD and MD, VD showed a higher number of PVS in basal ganglia and centrum semiovale (p=0.040), while MD showed more deep and juxtacortical MB (p=0.042 and p=0.022, respectively). No significant difference was observed in scores of cortical atrophy scales and Evans' index among the three groups.</p><p><strong>Conclusion: </strong>The proposed MRI protocol represents a useful advancement in the diagnostic assessment of patients with cognitive impairment by more accurately detecting vascular lesions, mainly microbleeds, without a significant increase in time and resource expenditure. Our findings confirm that white and grey matter lesions predominate in vascular and mixed dementia, whereas deep and juxtacortical microbleeds predominate in mixed dementia, suggesting that cerebral amyloid angiopathy could be the main underlying pathology.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 6","pages":"449-457"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10449486","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":"Effect of Simultaneous Dual-Task Training on Regional Cerebral Blood Flow in Older Adults with Amnestic Mild Cognitive Impairment.","authors":"Yota Kunieda,&nbsp;Chiaki Arakawa,&nbsp;Takumi Yamada,&nbsp;Shingo Koyama,&nbsp;Mizue Suzuki,&nbsp;Daisuke Ishiyama,&nbsp;Minoru Yamada,&nbsp;Ryuto Hirokawa,&nbsp;Tadamitsu Matsuda,&nbsp;Shintaro Nio,&nbsp;Tomohide Adachi,&nbsp;Haruhiko Hoshino,&nbsp;Toshiyuki Fujiwara","doi":"10.2174/1567205019666220627091246","DOIUrl":"https://doi.org/10.2174/1567205019666220627091246","url":null,"abstract":"<p><strong>Background: </strong>No previous study has examined the effect of dual-task training using changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) as an outcome.</p><p><strong>Objective: </strong>This study aimed to examine the effects of simultaneous dual-task training of exercise and cognitive tasks on rCBF using SPECT in older adults with amnestic mild cognitive impairment (aMCI).</p><p><strong>Methods: </strong>In this non-randomized control trial, 40 older adults with aMCI participated from May 2016 to April 2018. Outpatients in the intervention group (n = 22) underwent 24 sessions (12 months) of dualtask training twice a month for 60 mins per session. Participants in the control group (n = 18) continued to have regular outpatient visits. The primary outcome was rCBF at baseline and after 12 months, which was compared in each group using the two-sample t-test. The secondary outcomes were the rate of reversion and conversion from aMCI after 12 months.</p><p><strong>Results: </strong>Of the 22 participants in the intervention group, six dropped out; therefore, 16 were included in the analysis. The intervention group showed more significant increases in rCBF in multiple regions, including the bilateral frontal lobes, compared with the control group. However, the rates of reversion or conversion from mild cognitive impairment (MCI) were not significantly different.</p><p><strong>Conclusion: </strong>Dual-task training for older adults with aMCI increased rCBF in the frontal gyrus but did not promote reversion from MCI to normal cognition. Future intervention studies, such as follow-up examinations after the intervention, are warranted to consider long-term prognosis.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"458-468"},"PeriodicalIF":2.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40405925","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":"White Matter Damage in Alzheimer's Disease: Contribution of Oligodendrocytes.","authors":"Jinyu Zhou, Peng Zhang, Bo Zhang, Yuhan Kong","doi":"10.2174/1567205020666221021115321","DOIUrl":"10.2174/1567205020666221021115321","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an age-related neurodegenerative disease seriously influencing the quality of life and is a global health problem. Many factors affect the onset and development of AD, but specific mechanisms underlying the disease are unclear. Most studies investigating AD have focused on neurons and the gray matter in the central nervous system (CNS) but have not led to effective treatments. Recently, an increasing number of studies have focused on white matter (WM). Magnetic resonance imaging and pathology studies have shown different degrees of WM abnormality during the progression of AD. Myelin sheaths, the main component of WM in the CNS, wrap and insulate axons to ensure conduction of the rapid action potential and axonal integrity. WM damage is characterized by progressive degeneration of axons, oligodendrocytes (OLs), and myelin in one or more areas of the CNS. The contributions of OLs to AD progression have, until recently, been largely overlooked. OLs are integral to myelin production, and the proliferation and differentiation of OLs, an early characteristic of AD, provide a promising target for preclinical diagnosis and treatment. However, despite some progress, the key mechanisms underlying the contributions of OLs to AD remain unclear. Given the heavy burden of medical treatment, a better understanding of the pathophysiological mechanisms underlying AD is vital. This review comprehensively summarizes the results on WM abnormalities in AD and explores the relationship between OL progenitor cells and the pathogenesis of AD. Finally, the underlying molecular mechanisms and potential future research directions are discussed.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":" ","pages":"629-640"},"PeriodicalIF":1.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9391269","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":"Human microRNA-4433 (hsa-miR-4443) Targets 18 Genes to be a Risk Factor of Neurodegenerative Diseases.","authors":"Xing Ge,&nbsp;Tingting Yao,&nbsp;Chaoran Zhang,&nbsp;Qingqing Wang,&nbsp;Xuxu Wang,&nbsp;Li-Chun Xu","doi":"10.2174/1567205019666220805120303","DOIUrl":"https://doi.org/10.2174/1567205019666220805120303","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative diseases, such as Alzheimer's disease patients (AD), Huntington's disease (HD) and Parkinson's disease (PD), are common causes of morbidity, mortality, and cognitive impairment in older adults.</p><p><strong>Objective: </strong>We aimed to understand the transcriptome characteristics of the cortex of neurodegenerative diseases and to provide an insight into the target genes of differently expressed microRNAs in the occurrence and development of neurodegenerative diseases.</p><p><strong>Methods: </strong>The Limma package of R software was used to analyze GSE33000, GSE157239, GSE64977 and GSE72962 datasets to identify the differentially expressed genes (DEGs) and microRNAs in the cortex of neurodegenerative diseases. Bioinformatics methods, such as GO enrichment analysis, KEGG enrichment analysis and gene interaction network analysis, were used to explore the biological functions of DEGs. Weighted gene co-expression network analysis (WGCNA) was used to cluster DEGs into modules. RNA22, miRDB, miRNet 2.0 and TargetScan7 databases were performed to predict the target genes of microRNAs.</p><p><strong>Results: </strong>Among 310 Alzheimer's disease (AD) patients, 157 Huntington's disease (HD) patients and 157 non-demented control (Con) individuals, 214 co-DEGs were identified. Those co-DEGs were filtered into 2 different interaction network complexes, representing immune-related genes and synapserelated genes. The WGCNA results identified five modules: yellow, blue, green, turquoise, and brown. Most of the co-DEGs were clustered into the turquoise module and blue module, which respectively regulated synapse-related function and immune-related function. In addition, human microRNA-4433 (hsa-miR-4443), which targets 18 co-DEGs, was the only 1 co-up-regulated microRNA identified in the cortex of neurodegenerative diseases.</p><p><strong>Conclusion: </strong>214 DEGs and 5 modules regulate the immune-related and synapse-related function of the cortex in neurodegenerative diseases. Hsa-miR-4443 targets 18 co-DEGs and may be a potential molecular mechanism in neurodegenerative diseases' occurrence and development.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 7","pages":"511-522"},"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/4a/a5/CAR-19-511.PMC9906632.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10730727","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":"Random-Forest-Algorithm-Based Applications of the Basic Characteristics and Serum and Imaging Biomarkers to Diagnose Mild Cognitive Impairment.","authors":"Juan Yang,&nbsp;Haijing Sui,&nbsp;Ronghong Jiao,&nbsp;Min Zhang,&nbsp;Xiaohui Zhao,&nbsp;Lingling Wang,&nbsp;Wenping Deng,&nbsp;Xueyuan Liu","doi":"10.2174/1567205019666220128120927","DOIUrl":"https://doi.org/10.2174/1567205019666220128120927","url":null,"abstract":"<p><strong>Background: </strong>Mild cognitive impairment (MCI) is considered the early stage of Alzheimer's Disease (AD). The purpose of our study was to analyze the basic characteristics and serum and imaging biomarkers for the diagnosis of MCI patients as a more objective and accurate approach.</p><p><strong>Methods: </strong>The Montreal Cognitive Test was used to test 119 patients aged ≥65. Such serum biomarkers were detected as preprandial blood glucose, triglyceride, total cholesterol, Aβ1-40, Aβ1-42, and P-tau. All the subjects were scanned with 1.5T MRI (GE Healthcare, WI, USA) to obtain DWI, DTI, and ASL images. DTI was used to calculate the anisotropy fraction (FA), DWI was used to calculate the apparent diffusion coefficient (ADC), and ASL was used to calculate the cerebral blood flow (CBF). All the images were then registered to the SPACE of the Montreal Neurological Institute (MNI). In 116 brain regions, the medians of FA, ADC, and CBF were extracted by automatic anatomical labeling. The basic characteristics included gender, education level, and previous disease history of hypertension, diabetes, and coronary heart disease. The data were randomly divided into training sets and test ones. The recursive random forest algorithm was applied to the diagnosis of MCI patients, and the recursive feature elimination (RFE) method was used to screen the significant basic features and serum and imaging biomarkers. The overall accuracy, sensitivity, and specificity were calculated, respectively, and so were the ROC curve and the area under the curve (AUC) of the test set.</p><p><strong>Results: </strong>When the variable of the MCI diagnostic model was an imaging biomarker, the training accuracy of the random forest was 100%, the correct rate of the test was 86.23%, the sensitivity was 78.26%, and the specificity was 100%. When combining the basic characteristics, the serum and imaging biomarkers as variables of the MCI diagnostic model, the training accuracy of the random forest was found to be 100%; the test accuracy was 97.23%, the sensitivity was 94.44%, and the specificity was 100%. RFE analysis showed that age, Aβ1-40, and cerebellum_4_6 were the most important basic feature, serum biomarker, imaging biomarker, respectively.</p><p><strong>Conclusion: </strong>Imaging biomarkers can effectively diagnose MCI. The diagnostic capacity of the basic trait biomarkers or serum biomarkers for MCI is limited, but their combination with imaging biomarkers can improve the diagnostic capacity, as indicated by the sensitivity of 94.44% and the specificity of 100% in our model. As a machine learning method, a random forest can help diagnose MCI effectively while screening important influencing factors.</p>","PeriodicalId":10810,"journal":{"name":"Current Alzheimer research","volume":"19 1","pages":"76-83"},"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/b5/3d/CAR-19-76.PMC9189735.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39743447","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}