scholarly journals APOE GENE POLYMORPHISM: THE IMPACT OF APOE4 ALLELE ON SYSTEMIC INFLAMMATION AND ITS ROLE IN THE PATHOGENESIS OF ALZHEIMER’S DISEASE

2018 ◽  
Vol 20 (3) ◽  
pp. 303-312 ◽  
Author(s):  
I. K. Malashenkova ◽  
S. A. Krynskiy ◽  
M. V. Mamoshina ◽  
N. A. Didkovskiy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Systemic Inflammation ◽  
Apoe Gene ◽  
Apoe4 Allele ◽  
The Impact ◽  
Apoe Gene Polymorphism

The Application Value of ApoE Gene Polymorphism in Alzheimer's Disease

2019 ◽  
Vol 9 (10) ◽  
pp. 1403-1407
Author(s):  
Cong Chen ◽  
Yuhui Zhang ◽  
Bin Chen ◽  
Chaosheng Zeng ◽  
Min Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Apoe Genotype ◽  
Apoe Gene ◽  
Control Group ◽  
Apolipoprotein E Polymorphism ◽  
Abnormal Lipid Metabolism ◽  
And Control ◽  
Apoe Gene Polymorphism

To explore the association of apolipoprotein E polymorphism with Alzheimer's disease (AD), so as to provide possible research value for potential targeted therapy. 120 AD patients and 50 healthy volunteers were enrolled to extract fasting blood samples. ApoE gene polymorphism and blood lipids were tested in blood. ApoE gene and genotype frequency between AD group and control group were compared by PCR and sequencing methods. MMSE, CDR, and BPSD were used to determine the intelligence. ApoE genotype was detected by DNA microarray. ɛ4 carrier accounted for 45% in AD group, which was significantly elevated compared with control group (12%) (P < 0.05). TG, TC, and LDL-C levels were increased, while HDL-C was reduced in ɛ4 allele carriers (allP < 0.05). The MMSE scores of ApoEɛ4 genotype carriers in AD group were markedly lower than those of nonApoEɛ4 genotype carriers (P < 0.05) and control (P < 0.01). The proportion of dementia in ApoEɛ4 genotype carriers from AD group was apparently higher than the ɛ4 gene non-carriers (P < 0.05). The ApoEɛ4 gene is an AD risk factor. The changes of genotype and frequency of ApoEɛ4 gene are the main factors leading to abnormal lipid metabolism in AD patients, suggesting that ApoEɛ4 gene detection might be helpful for the early diagnosis and treatment of AD.

scholarly journals A CROSS-SECTIONAL ANALYSIS OF APOE GENE POLYMORPHISM AND THE RISK OF COGNITIVE IMPAIRMENTS IN THE ALZHEIMER’S DISEASE NEUROIMAGING INITIATIVE STUDY

2021 ◽  
pp. 1-6
Author(s):  
G. Wang ◽  
D.E. Vance ◽  
W. Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Cognitive Impairments ◽  
Apoe Genotype ◽  
Apoe Gene ◽  
Dependent Manner ◽  
Cross Sectional ◽  
Apoe Genotypes ◽  
Apoe Gene Polymorphism

Background: It is inconclusive on how apolipoprotein epsilon (APOE) gene polymorphism is associated with the risk of having mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Objectives: To investigate how APOE genotype is associated with the risk of MCI or AD using the data collected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants. Methods: A cross-sectional design was used to analyze the baseline data collected from the 1,720 ADNI participants. APOE gene polymorphism was analyzed on how they are related to the risk of cognitive impairments of either MCI or AD using a percent yield (PY) method. Then cognitive functions were compared among six different APOE genotypes using a two-way ANCOVA by controlling possible confounding factors. Results: The prevalence of six APOE genotypes in 1,720 participants is as following: e2/e2 (0.3%), e2/e3 (7.4%), e3/e3 (45.4%), e2/e4 (2%), e3/e4 (35%) and e4/e4 (9.9%). The e2/e2 and e4/e4 genotypes were associated with the lowest and the highest risk respectively for cognitive impairments of either MCI or AD. Further, a worse cognitive diagnosis was associated with an increasing number of APOE e4 allele in a dose dependent manner. Participants with genotype e3/e3 had a better memory measure than those with the genotype of e3/e4. Conclusions: APOE gene polymorphism is associated with different level of risks for cognitive impairments. The heterozygous genotype e3/e4 is associated with a worse memory function compared to the genotype of e3/e3. Further investigations are needed to intervene the cognitive deteriorations in those with at risk APOE genotypes.

scholarly journals Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Luke Whiley ◽  
◽  
Katie E. Chappell ◽  
Ellie D’Hondt ◽  
Matthew R. Lewis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Systemic Inflammation ◽  
Metabolic Phenotyping ◽  
Acid Urine ◽  
Metabolite Concentrations ◽  
Ssri Medication ◽  
The Impact ◽  
Urine And Serum ◽  
Urine Serum

Abstract Background Both serotonergic signalling disruption and systemic inflammation have been associated with the pathogenesis of Alzheimer’s disease (AD). The common denominator linking the two is the catabolism of the essential amino acid, tryptophan. Metabolism via tryptophan hydroxylase results in serotonin synthesis, whilst metabolism via indoleamine 2,3-dioxygenase (IDO) results in kynurenine and its downstream derivatives. IDO is reported to be activated in times of host systemic inflammation and therefore is thought to influence both pathways. To investigate metabolic alterations in AD, a large-scale metabolic phenotyping study was conducted on both urine and serum samples collected from a multi-centre clinical cohort, consisting of individuals clinically diagnosed with AD, mild cognitive impairment (MCI) and age-matched controls. Methods Metabolic phenotyping was applied to both urine (n = 560) and serum (n = 354) from the European-wide AddNeuroMed/Dementia Case Register (DCR) biobank repositories. Metabolite data were subsequently interrogated for inter-group differences; influence of gender and age; comparisons between two subgroups of MCI - versus those who remained cognitively stable at follow-up visits (sMCI); and those who underwent further cognitive decline (cMCI); and the impact of selective serotonin reuptake inhibitor (SSRI) medication on metabolite concentrations. Results Results revealed significantly lower metabolite concentrations of tryptophan pathway metabolites in the AD group: serotonin (urine, serum), 5-hydroxyindoleacetic acid (urine), kynurenine (serum), kynurenic acid (urine), tryptophan (urine, serum), xanthurenic acid (urine, serum), and kynurenine/tryptophan ratio (urine). For each listed metabolite, a decreasing trend in concentrations was observed in-line with clinical diagnosis: control > MCI > AD. There were no significant differences in the two MCI subgroups whilst SSRI medication status influenced observations in serum, but not urine. Conclusions Urine and serum serotonin concentrations were found to be significantly lower in AD compared with controls, suggesting the bioavailability of the neurotransmitter may be altered in the disease. A significant increase in the kynurenine/tryptophan ratio suggests that this may be a result of a shift to the kynurenine metabolic route due to increased IDO activity, potentially as a result of systemic inflammation. Modulation of the pathways could help improve serotonin bioavailability and signalling in AD patients.

The Impact of APOE Status on Relationship of Biomarkers of Vascular Risk and Systemic Inflammation to Neuropsychiatric Symptoms in Alzheimer's Disease

2014 ◽  
Vol 40 (4) ◽  
pp. 887-896 ◽  
Author(s):  
James R. Hall ◽  
April R. Wiechmann ◽  
Leigh A. Johnson ◽  
Melissa Edwards ◽  
Robert C. Barber ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Systemic Inflammation ◽  
Neuropsychiatric Symptoms ◽  
Vascular Risk ◽  
Relationship Of ◽  
The Impact

scholarly journals Apolipoprotein E Polymorphism and Alzheimer’s Risk in Kashmiri Population

2021 ◽  
Vol 18 (4) ◽  
pp. 673-680
Author(s):  
Kamran Nissar ◽  
Arshad Hussain ◽  
Bashir Ahmad Ganai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Polymorphism ◽  
Apoe Gene ◽  
Gene Variation ◽  
Variant Genotype ◽  
Apolipoprotein E Polymorphism ◽  
Survey Results ◽  
Kashmiri Population

Background: Although the cause of Alzheimer's disease is unknown, most experts feel that the disease is caused by a combination of circumstances rather than a single cause. Age, gene polymorphism, diabetes, and other conditions are all risk factors for Alzheimer's disease. Given the importance of gene polymorphism in different diseases, we intended to find out the association of APOE gene polymorphism with Alzheimer's risk in the Kashmiri population. Method: Out of 300 patients who were referred to the memory clinic of the hospital, to evaluate the probable relation of APOE gene variation in Alzheimer's disease, we conducted the study on 59 clinically confirmed Alzheimer's patients and 52 age and ethnicity-matched healthy controls found in a community survey. Results: Our data revealed a statistically significant association of ε4 variant genotype of the APOE gene with AD susceptibility in the Kashmiri population. Conclusions: The current study's findings provided insight into the role of APOE polymorphisms in Alzheimer's disease susceptibility. The identified susceptibility variant may become a marker genotype for AD.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

Emerging Proof of Protein Misfolding and Interactions in Multifactorial Alzheimer's Disease

2020 ◽  
Vol 20 (26) ◽  
pp. 2380-2390 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Abdullah Al Mamun ◽  
Md. Ataur Rahman ◽  
Tapan Behl ◽  
Asma Perveen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Misfolding ◽  
Neurodegenerative Disorder ◽  
Senile Plaques ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Misfolded Proteins ◽  
Cell Organelles ◽  
The Impact

Objective: Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by the extracellular accumulations of amyloid beta (Aβ) as senile plaques and intracellular aggregations of tau in the form of neurofibrillary tangles (NFTs) in specific brain regions. In this review, we focus on the interaction of Aβ and tau with cytosolic proteins and several cell organelles as well as associated neurotoxicity in AD. Summary: Misfolded proteins present in cells accompanied by correctly folded, intermediately folded, as well as unfolded species. Misfolded proteins can be degraded or refolded properly with the aid of chaperone proteins, which are playing a pivotal role in protein folding, trafficking as well as intermediate stabilization in healthy cells. The continuous aggregation of misfolded proteins in the absence of their proper clearance could result in amyloid disease including AD. The neuropathological changes of AD brain include the atypical cellular accumulation of misfolded proteins as well as the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. The mechanism of neurodegeneration in AD that leads to severe neuronal cell death and memory dysfunctions is not completely understood until now. Conclusion: Examining the impact, as well as the consequences of protein misfolding, could help to uncover the molecular etiologies behind the complicated AD pathogenesis.

scholarly journals Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna A. Lauer ◽  
Daniel Janitschke ◽  
Malena dos Santos Guilherme ◽  
Vu Thu Thuy Nguyen ◽  
Cornel M. Bachmann ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Lipid Homeostasis ◽  
Medical Surveillance ◽  
Shotgun Lipidomics ◽  
App Processing ◽  
Cognitive Improvement ◽  
The Impact

AbstractAlzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients.

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