scholarly journals Allelic Distribution of Genes for Apolipoprotein E and MTHFR in Patients with Alzheimer’s Disease and Their Epistatic Interaction

2020 ◽  
Vol 77 (3) ◽  
pp. 1095-1105
Author(s):  
Stanislav Sutovsky ◽  
Robert Petrovic ◽  
Maria Fischerova ◽  
Viera Haverlikova ◽  
Barbara Ukropcova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Epistatic Interaction ◽  
Methylenetetrahydrofolate Reductase ◽  
Specific Gene ◽  
Dependent Manner ◽  
Study Results ◽  
E4 Allele ◽  
Dose Dependent

Background: Genetic risk factors play an important role in the pathogenesis of Alzheimer’s disease (AD). However, the gene-gene interaction (epistasis) between specific allelic variants is only partially understood. Objective: In our study, we examined the presence of the ɛ4 allele of apolipoprotein E (APOE) and the presence of C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with AD and controls. We also evaluated the epistatic interaction between MTHFR and the APOE variants. Methods: A total of 564 patients with AD and 534 cognitively unimpaired age-matched controls were involved in the study. Results: The presence of the ɛ4 allele of APOE increases the risk of developing AD in a dose-dependent manner (OR 32.7: homozygotes, 15.6: homozygotes + heterozygotes, 14.3: heterozygotes). The combination of genotypes also increases the risk of developing AD in a dose-dependent manner: OR 18.3 (APOE 4/X and 4/4 + CT rs1801133), OR 19.4 (APOE 4/X and 4/4 + CT rs1801133 + AC rs1801131), OR 22.4 (APOE 4/X and 4/4 + TT rs1801133), and OR 21.2 (APOE 4/X and 4/4 + CC rs1801131). Homozygotes for variant alleles of MTHFR as well as patients with AD had significantly higher levels of homocysteine than homozygotes for standard alleles or controls. Conclusion: Homozygotes for APOE4 and carriers of APOE4 with TT genotype of rs1801133 were found to be at the highest risk of developing AD. These findings suggest that the epistatic interaction of specific gene variants can have a significant effect on the development of AD.

scholarly journals Green Tea Seed Isolated Theasaponin E1 Ameliorates AD Promoting Neurotoxic Pathogenesis by Attenuating Aβ Peptide Levels in SweAPP N2a Cells

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2334 ◽  
Author(s):  
Muhammad Imran Khan ◽  
Jin Hyuk Shin ◽  
Min Yong Kim ◽  
Tai Sun Shin ◽  
Jong Deog Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Green Tea ◽  
Neuroblastoma Cells ◽  
Dependent Manner ◽  
Insulin Degrading Enzyme ◽  
App Processing ◽  
N2a Cells ◽  
Gene And Protein Expression ◽  
Dose Dependent

Alzheimer’s disease (AD) is the most frequent type of dementia affecting memory, thinking and behaviour. The major hallmark of the disease is pathological neurodegeneration due to abnormal aggregation of Amyloid beta (Aβ) peptides generated by β- and γ-secretases via amyloidogenic pathway. Purpose of the current study was to evaluate the effects of theasaponin E1 on the inhibition of Aβ producing β-, γ-secretases (BACE1, PS1 and NCT) and acetylcholinesterase and activation of the non-amyloidogenic APP processing α-secretase (ADAM10). Additionally, theasaponin E1 effects on Aβ degrading and clearing proteins neprilysin and insulin degrading enzyme (IDE). The effect of theasaponin E1 on these crucial enzymes was investigated by RT-PCR, ELISA, western blotting and fluorometric assays using mouse neuroblastoma cells (SweAPP N2a). theasaponin E1 was extracted and purified from green tea seed extract via HPLC, and N2a cells were treated with different concentrations for 24 h. Gene and protein expression in the cells were measured to determine the effects of activation and/or inhibition of theasaponin E1 on β- and γ-secretases, neprilysin and IDE. Results demonstrated that theasaponin E1 significantly reduced Aβ concentration by activation of the α-secretase and neprilysin. The activities of β- and γ-secretase were reduced in a dose-dependent manner due to downregulation of BACE1, presenilin, and nicastrin. Similarly, theasaponin E1 significantly reduced the activity of acetylcholinesterase. Overall, from the results it is concluded that green tea seed extracted saponin E1 possess therapeutic significance as a neuroprotective natural product recommended for the treatment of Alzheimer’s disease.

750 On the genetic contribution of Apolipoprotein E e4 allele in Alzheimer's disease transmission

1996 ◽  
Vol 17 (4) ◽  
pp. S186
Author(s):  
M. Martinez ◽  
D. Campion ◽  
D. Hannequin ◽  
A. Brice ◽  
T. Freebourg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Disease Transmission ◽  
Genetic Contribution ◽  
E4 Allele

scholarly journals Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

2006 ◽  
Vol 32 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Kristina F Zdanys ◽  
Timothy G Kleiman ◽  
Martha G MacAvoy ◽  
Benjamin T Black ◽  
Tracy E Rightmer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Psychotic Symptoms ◽  
E4 Allele

Association between apolipoprotein E e4 allele and apathy in probable Alzheimer's disease.

2006 ◽  
Vol 113 (1) ◽  
pp. 59-63 ◽  
Author(s):  
R. Monastero ◽  
E. Mariani ◽  
C. Camarda ◽  
T. Ingegni ◽  
M. R. Averna ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
E4 Allele

Effect of Plant Compound Curcumin on the Expression of a-Synuclein in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

2013 ◽  
Vol 781-784 ◽  
pp. 643-646
Author(s):  
Xiao Lin ◽  
Li Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Dependent Manner ◽  
Double Transgenic Mice ◽  
Ad Alzheimer’S Disease ◽  
Dose Dependent

In this study, we aim to investigate the effect of curcumin on the expression of a-synuclein in the APPswe/PS1dE9 double transgenic mice. APPswe/PS1dE9 double transgenic mice were used as AD (Alzheimer's disease) model and fed with different concentrations of curcumin every day for 6 months, then immunohistochemistry method were used to detect the expression of a-synuclein in hippocampus of mice. The expression of a-syn in hippocampal neuron was decreased significantly after treated with 0.16g/kg to 1.0g/kg curcumin, the change was apparent in dose-dependent manner (P<0.05). a-synuclein pay an important role in the genesis and development of Alzheimer's disease and decreased level of a-synuclein might contribute to the neuroprotective effect of Curcumin, which may become a new target for the prevention and treatment of Alzheimer's disease.

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