scholarly journals Association of MS4A6A, CD33, and TREM2 gene polymorphisms with the late-onset Alzheimer’s disease

Bioimpacts ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 219-225 ◽  
Author(s):  
Elham Mehdizadeh ◽  
Mohammad Khalaj-Kondori ◽  
Zeinab Shaghaghi-Tarakdari ◽  
Saeed Sadigh-Eteghad ◽  
Mahnaz Talebi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphisms ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Salting Out ◽  
Age And Gender ◽  
Blood Samples ◽  
Significant Difference ◽  
And Gender

Introduction: Alzheimer’s disease (AD), which is a progressive neurodegenerative disorder, causes structural and functional brain disruption. MS4A6A, TREM2, and CD33 gene polymorphisms loci have been found to be associated with the pathobiology of late-onset AD (LOAD). In the present study, we tested the hypothesis of association of LOAD with rs983392, rs75932628, and rs3865444 polymorphisms in MS4A6A, TREM2, CD33 genes, respectively.Methods: In the present study, 113 LOAD patients and 100 healthy unrelated age- and gender-matched controls were selected. DNA was extracted from blood samples by the salting-out method and the genotyping was performed by RFLP-PCR. Electrophoresis was carried out on agarose gel. Sequencing was thereafter utilized for the confirmation of the results. Results: Only CD33 rs3865444 polymorphism revealed a significant difference in the genotypic frequencies of GG (P = 0.001) and GT (P = 0.001), and allelic frequencies of G (P = 0.033) and T (P = 0.03) between LOAD patients and controls. Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population.

scholarly journals Investigation of five polymorphic DNA markers associated with late onset Alzheimer disease

Genetika ◽  
2013 ◽  
Vol 45 (2) ◽  
pp. 503-514 ◽  
Author(s):  
Jalal Gharesouran ◽  
Maryam Rezazadeh ◽  
Mohaddes Mojtaba
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Markers ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
The Elderly ◽  
Healthy Controls ◽  
Genotype Frequencies ◽  
Significant Difference ◽  
And Control

Alzheimer's disease is a complex neurodegenerative disorder characterized by memory and cognitive impairment and is the leading cause of dementia in the elderly. The aim of our study was to examine the polymorphic DNA markers CCR2 (+190 G/A), CCR5?32, TNF-? (-308 G/A), TNF-? (-863 C/A) and CALHM1 (+394 C/T) to determine the relationship between these polymorphisms and the risk of late onset Alzheimer's disease in the population of Eastern Azerbaijan of Iran. A total of 160 patient samples and 163 healthy controls were genotyped by PCR-RFLP and the results confirmed using bidirectional sequencing. Statistical analysis of obtained data revealed non-significant difference between frequency of CCR5?32 in case and control groups. The same result was observed for TNF-? (-863 C/A) genotype and allele frequencies. Contrary to above results, significant differences were detected in frequency of TNF-? (-308 G/A) and CCR2-64I genotypes between the cases and healthy controls. A weak significant difference observed between allele and genotype frequencies of rs2986017 in CALHM1 (+394 C/T; P86L) in patient and control samples. It can be concluded that the T allele of P86L variant in CALHM1 & +190 G/A allele of CCR2 have a protective role against abnormal clinical features of Alzheimer's disease.

scholarly journals C-338A Polymorphism of the Endothelin-Converting Enzyme (ECE-1) Gene and the Susceptibility to Sporadic Late-Onset Alzheimer’s Disease and Coronary Artery Disease

2008 ◽  
Vol 24 (3) ◽  
pp. 175-179 ◽  
Author(s):  
Renato Scacchi ◽  
Giuseppe Gambina ◽  
Elisabetta Broggio ◽  
Maria Ruggeri ◽  
Rosa Maria Corbo
Keyword(s):  
Alzheimer’S Disease ◽  
Coronary Artery Disease ◽  
Alzheimer's Disease ◽  
Coronary Artery ◽  
Late Onset ◽  
Protective Role ◽  
Converting Enzyme ◽  
Significant Difference ◽  
Endothelin Converting Enzyme ◽  
Artery Disease

The human endothelin-converting enzyme (ECE) is involved inβ-amyloid synthesis and regulation of the endothelin-1 (ET-1) vasoconstricting peptide. We investigated the distribution of the C-338A polymorphism of the ECE-1b gene in sporadic late-onset Alzheimer’s disease (LOAD) and in coronary artery disease (CAD) to verify its role in the onset of these two complex diseases. Two cohorts of 458 Italian Caucasian LOAD patients and 165 CAD patients were examined for the C-338A polymorphism and compared with respective control samples (260 and 106 subjects, respectively). The A allele was less present in LOAD patients than in controls, but an at limits statistically significant difference was achieved only in subjects aged less than 80 years, where only the AA genotypes appeared to have a protective role against the onset of the sporadic LOAD. For the overall CAD sample the pattern was similar and significant differences were observed only in subjects non carrying the apolipoprotein E (APOE) e*4 allele, where the A allele carrying genotypes had a protective role against the onset of the disease.

Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-21
Author(s):  
Masoud Neshan ◽  
Seyed Kazem Malakouti ◽  
Leila Kamalzadeh ◽  
Mina Makvand ◽  
Arezoo Campbell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcription Factors ◽  
T Cell ◽  
Late Onset ◽  
Cytokine Gene Expression ◽  
Mrna Levels ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Background: Late-onset Alzheimer’s disease (LOAD) is associated with many environmental and genetic factors. The effect of systemic inflammation on the pathogenesis of neurodegenerative diseases such as AD has been strongly suggested. T helper cells (Th) are one of the important components of the immune system and can easily infiltrate the brain in pathological conditions. The development of each Th-subset depends on the production of unique cytokines and their main regulator. Objective: This study aimed to compare the mRNA levels of Th-related genes derived from peripheral blood mononuclear cells of LOAD patients with control. Also, the identification of the most important Th1/Th2 genes and downstream pathways that may be involved in the pathogenesis of AD was followed by computational approaches. Methods: This study invloved 30 patients with LOAD and 30 non-demented controls. The relative expression of T-cell cytokines (IFN-γ, TNF-α, IL-4, and IL-5) and transcription factors (T-bet and GATA-3) were assessed using real-time PCR. Additionally, protein-protein interaction (PPI) was investigated by gene network construction. Results: A significant decrease at T-bet, IFN-γ, TNF-α, and GATA-3 mRNA levels was detected in the LOAD group, compared to the controls. However, there was no significant difference in IL-4 or IL-5 mRNA levels. Network analysis revealed a list of the highly connected protein (hubs) related to mitogen-activated protein kinase (MAPK) signaling and Th17 cell differentiation pathways. Conclusion: The findings point to a molecular dysregulation in Th-related genes, which can promising in the early diagnosis or targeted interventions of AD. Furthermore, the PPI analysis showed that upstream off-target stimulation may involve MAPK cascade activation and Th17 axis induction.

scholarly journals Association and Gene–-Gene Interactions Study of Late-Onset Alzheimer’s Disease in the Russian Population

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1647
Author(s):  
Anna Bocharova ◽  
Kseniya Vagaitseva ◽  
Andrey Marusin ◽  
Natalia Zhukova ◽  
Irina Zhukova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Factor Model ◽  
Late Onset ◽  
Interaction Network ◽  
Russian Population ◽  
Protein Protein Interaction ◽  
Protective Haplotype ◽  
Single Snps

Alzheimer’s disease (AD) is a neurodegenerative disorder, and represents the most common cause of dementia. In this study, we performed several different analyses to detect loci involved in development of the late onset AD in the Russian population. DNA samples from 472 unrelated subjects were genotyped for 63 SNPs using iPLEX Assay and real-time PCR. We identified five genetic loci that were significantly associated with LOAD risk for the Russian population (TOMM40 rs2075650, APOE rs429358 and rs769449, NECTIN rs6857, APOE ε4). The results of the analysis based on comparison of the haplotype frequencies showed two risk haplotypes and one protective haplotype. The GMDR analysis demonstrated three significant models as a result: a one-factor, a two-factor and a three-factor model. A protein–protein interaction network with three subnetworks was formed for the 24 proteins. Eight proteins with a large number of interactions are identified: APOE, SORL1, APOC1, CD33, CLU, TOMM40, CNTNAP2 and CACNA1C. The present study confirms the importance of the APOE-TOMM40 locus as the main risk locus of development and progress of LOAD in the Russian population. Association analysis and bioinformatics approaches detected interactions both at the association level of single SNPs and at the level of genes and proteins.

scholarly journals Novel Trends in Electrochemical Biosensors for Early Diagnosis of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Pavla Valkova ◽  
Miroslav Pohanka
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Disorder ◽  
Electrochemical Biosensors ◽  
Standard Laboratory ◽  
Blood Samples ◽  
Number Of Patients ◽  
Asymptomatic Phase ◽  
The Right

Background. Alzheimer’s disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder affecting mainly the population over 65 years of age. It is becoming a global health and socioeconomic problem, and the current number of patients reaching 30–50 million people will be three times higher over the next thirty years. Objective. Late diagnosis caused by decades of the asymptomatic phase and invasive and cost-demanding diagnosis are problems that make the whole situation worse. Electrochemical biosensors could be the right tool for less invasive and inexpensive early diagnosis helping to reduce spend sources— both money and time. Method. This review is a survey of the latest advances in the design of electrochemical biosensors for the early diagnosis of Alzheimer’s disease. Biosensors are divided according to target biomarkers. Conclusion. Standard laboratory methodology could be improved by analyzing a combination of currently estimated markers along with neurotransmitters and genetic markers from blood samples, which make the test for AD diagnosis available to the wide public.

scholarly journals Searching for novel cerebrospinal fluid biomarkers of tau pathology in frontotemporal dementia: an elusive quest

2019 ◽  
Vol 90 (7) ◽  
pp. 740-746 ◽  
Author(s):  
Martha S Foiani ◽  
Claudia Cicognola ◽  
Natalia Ermann ◽  
Ione O C Woollacott ◽  
Carolin Heller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Frontotemporal Dementia ◽  
Neurodegenerative Disorder ◽  
The Novel ◽  
Tau Pathology ◽  
Total Tau ◽  
Significant Difference ◽  
T Tau

BackgroundFrontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly associated with Alzheimer’s disease pathology. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species within cerebrospinal fluid (CSF) as biomarkers for tau pathology in FTD.Methods86 participants were included: 66 with a clinical diagnosis within the FTD spectrum and 20 healthy controls. Immunoassays targeting tau fragments N-123, N-mid-region, N-224 and X-368, as well as a non-phosphorylated form of tau were measured in CSF, along with total-tau (T-tau) and phospho-tau (P-tau(181)). Patients with FTD were grouped based on their Aβ42 level into those likely to have underlying Alzheimer’s disease (AD) pathology (n=21) and those with likely frontotemporal lobar degeneration (FTLD) pathology (n=45). The FTLD group was then subgrouped based on their underlying clinical and genetic diagnoses into those with likely tau (n=7) or TDP-43 (n=18) pathology.ResultsSignificantly higher concentrations of tau N-mid-region, tau N-224 and non-phosphorylated tau were seen in both the AD group and FTLD group compared with controls. However, none of the novel tau species showed a significant difference between the AD and FTLD groups, nor between the TDP-43 and tau pathology groups. In a subanalysis, normalising for total-tau, none of the novel tau species provided a higher sensitivity and specificity to distinguish between tau and TDP-43 pathology than P-tau(181)/T-tau, which itself only had a sensitivity of 61.1% and specificity of 85.7% with a cut-off of <0.109.ConclusionsDespite investigating multiple novel CSF tau fragments, none show promise as an FTD biomarker and so the quest for in vivo markers of FTLD-tau pathology continues.

scholarly journals Heterogeneity in Cost-Effectiveness Analysis of Vaccination for Mild and Moderate Alzheimer’s Disease

2019 ◽  
Vol 16 (6) ◽  
pp. 495-504
Author(s):  
Chung-Hsien Lin ◽  
Jean Ching-Yuan Fann ◽  
Sam Li-Sheng Chen ◽  
Hsiu-Hsi Chen ◽  
Kuen-Cheh Yang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cost Effectiveness ◽  
Age Groups ◽  
Cost Effectiveness Analysis ◽  
Age And Gender ◽  
Effectiveness Analysis ◽  
Population Average ◽  
Life Years ◽  
And Gender

Background:Immunotherapy for Alzheimer’s disease(AD) has gained momentum in recent years. One of the concerns over its application pertains to Cost-Effectiveness Analysis (CEA) from population average and specific subgroup differences, as such a therapy is imperative for health decisionmakers to allocate limited resources. However, this sort of CEA model considering heterogeneous population with risk factors adjustment has been rarely addressed.Methods:We aimed to show the heterogeneity of CEA in immunotherapy for AD in comparison with the comparator without intervention. Economic evaluation was performed via incremental Cost- Effectiveness Ratio (ICER) and Cost-Effectiveness Acceptability Curve (CEAC) in terms of the Quality- Adjusted Life Years (QALY). First, population-average CEA was performed with and without adjustment for age and gender. Secondly, sub-group CEA was performed with the stratification of gender and age based on Markov process.Results:Given the threshold of $20,000 of willingness to pay, the results of ICER without and with adjustment for age and gender revealed similar results ($14,691/QALY and $17,604/QALY). The subgroup ICER results by different age groups and gender showed substantial differences. The CEAC showed that the probability of being cost-effective was only 48.8%-53.3% in terms of QALY at population level but varied from 83.5% in women aged 50-64 years, following women aged 65-74 years and decreased to 0.2% in men≥ 75 years.Conclusion:There were considerable heterogeneities observed in the CEA of vaccination for AD. As with the development of personalized medicine, the CEA results assessed by health decision-maker should not only be considered by population-average level but also specific sub-group levels.

Association of Clusterin Gene Polymorphisms with Late-Onset Alzheimer’s Disease

2011 ◽  
Vol 32 (3) ◽  
pp. 198-201 ◽  
Author(s):  
Huiying Gu ◽  
Xing Wei ◽  
Shirley Chen ◽  
Alexander Kurz ◽  
Ulrich Müller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphisms ◽  
Late Onset

scholarly journals The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Troy T. Rohn
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Neurodegenerative Disorder ◽  
Late Onset ◽  
Senile Plaques ◽  
Myeloid Cells ◽  
Disease Process ◽  
Age Related

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by a progressive loss of memory and cognitive skills. Although much attention has been devoted concerning the contribution of the microscopic lesions, senile plaques, and neurofibrillary tangles to the disease process, inflammation has long been suspected to play a major role in the etiology of AD. Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD. Variants in TREM2 triple one's risk of developing late-onset AD. TREM2 is expressed on microglial cells, the resident macrophages in the CNS, and functions to stimulate phagocytosis on one hand and to suppress cytokine production and inflammation on the other hand. The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS. In this context, an overview of the pathways linking beta-amyloid, neurofibrillary tangles (NFTs), oxidative stress, and inflammation will be discussed.

An Electroencephalographic Investigation of Late-Onset Schizophrenia

1999 ◽  
Vol 11 (4) ◽  
pp. 421-429 ◽  
Author(s):  
Perminder Sachdev ◽  
Henry Brodaty ◽  
Sophia Roubina ◽  
Roderick A. Mackenzie
Keyword(s):  
Late Onset ◽  
Control Group ◽  
Neuroleptic Drugs ◽  
Schizophrenic Disorder ◽  
Age And Gender ◽  
Significant Difference ◽  
The Subject ◽  
Community Controls ◽  
And Gender ◽  
Healthy Community

We performed awake and resting electroencephalograms (EEGs) on 22 subjects with DSM-III-R schizophrenic disorder of late onset (at or after age 50 years), and compared them with the EEGs of 33 healthy community controls matched for age and gender. The EEGs were rated qualitatively and a 2-minute, artifact-free tracing from each subject was quantified manually by an experienced neurophysiologist unaware of the identity of the subject group. The only significant difference was the presence of more generalized slowing in the EEGs of schizophrenia patients, which was at least partially accounted for by the effect of neuroleptic drugs. The schizophrenic subjects did not have a greater prevalence of epileptiform disturbances or abnormal asymmetry of the EEG compared to the control group. Our study does not suggest the presence of underlying dementia in schizophrenia of late onset.

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