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

Author(s):  
G. Wang ◽  
D.E. Vance ◽  
W. Li

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.

2019 ◽  
Vol 9 (10) ◽  
pp. 1403-1407
Author(s):  
Cong Chen ◽  
Yuhui Zhang ◽  
Bin Chen ◽  
Chaosheng Zeng ◽  
Min Chen ◽  
...  

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.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
ZhiZhong Wang ◽  
Wanrui Ma ◽  
Ye Rong ◽  
Lan Liu

The association, in different ethnic groups, of apolipoprotein E (apoE) gene polymorphism with mild cognitive impairment (MCI) has been unclear. Few studies have examined the association in Chinese minorities. The current study explores the association between apoE gene polymorphism and MCI in one of the biggest ethnic groups—the Hui—and compares it with the Han. The Minimental State Exam, Activities of Daily Living Scale, and Geriatric Depression Scale were administered to 306 ethnic Hui and 618 ethnic Han people aged≥55 years. ApoE genotypes were determined using the high resolution melting curve method. The distribution of the apoE genotype and the frequency of allelesε2,ε3, andε4 were similar in the Hui and Han groups. In analyses adjusted for age, gender, and education level, theε4 allele was a risk factor for MCI in both the Hui group (OR=2.61, 95% CI: 1.02–6.66) and the Han group (OR=2.36, 95% CI: 1.19–4.67), but the apoEε2 allele was protective for MCI only in the Han group (OR=0.48, 95% CI: 0.38–0.88). The association of some apoE genotypes with MCI may differ in different ethnic groups in China. Further studies are needed to explore this effect among different populations.


2021 ◽  
pp. 1-10
Author(s):  
Wei Qin ◽  
Wenwen Li ◽  
Qi Wang ◽  
Min Gong ◽  
Tingting Li ◽  
...  

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.


2020 ◽  
Vol 23 (81) ◽  
pp. 130-139
Author(s):  
G. Pšemeneckienė ◽  
K. Petrikonis ◽  
D. Rastenytė

Įvadas. Yra duomenų, kad IL1α ir IL6, kaip vienų svarbiausių citokinų, dalyvaujančių neurouždegimo procesuose, genų polimorfizmai yra susiję su Alzheimerio ligos (AL) rizika. Šiame tyrime siekėme įvertinti IL1A -889C>T ir IL6 -174G>C polimorfizmų sąsajas su sporadinės AL rizika APOE ε4 nešiotojams ir APOE rizikos alelio neturintiems asmenims. Taip pat tyrėme IL1A -889C>T ir IL6 -174G>C polimorfizmų sąsajas su AL progresavimo pobūdžiu. Tiriamieji ir tyrimo metodai. Tyrime dalyvavo 110 sergančiųjų sporadine AL ir 115 sutapatintų pagal amžių ir lytį sveikų kontrolinių tiriamųjų, kurių pažinimo funkcijos nesutrikusios (Lietuvos populiacija). IL1A -889C>T (rs1800587) ir IL6 -174G>C (rs1800795, Intro- no tipo) genotipavimas atliktas tikro laiko PGR (TL-PGR) metodu. Rezultatai. IL1A -889C>T genotipų dažniai APOE4+ grupėje (C/C – 52,9 %, C/T – 41,2 %, T/T – 5,9 %), lyginant su APOE4- sergančiaisiais AL (C/C – 55,6 %, C/T – 37,0 %, T/T – 7,4 %), nesiskyrė (p = 0,887). Sergantiems AL pacientams IL6 -174G>C genotipai APOE4+ grupėje (G/G – 11,8 %, G/C – 62,7 %, C/C – 25,5 %) ir APOE4- grupėje (G/G – 14,8 %, G/C – 61,1 %, C/C – 24,1 %) buvo pasiskirstę panašiai (p = 0,898). Genotipų dažniai reikšmingai nesiskyrė sergantiesiems greitai progresuojančia AL, lyginant su lėtai progresuojančia AL (p (IL1A -889C>T) = 0,638; p (IL6 -174G>C) = 0,118). IL1A -889C>T ir IL6 -174G>C polimorfizmų paveldėjimas (dominantinio, overdominantinio ir recesyvinio modeli0), atsižvelgiant į APOE genotipą, reikšmingai nekeitė galimybių santykio sirgti AL (p < 0,05). Lėtai ir greitai progresuojančios AL grupėse IL1A -889C>T ir IL6 -174G>C polimorfizmų paveldėjimas AL galimybei reikšmingos įtakos neturėjo (p < 0,05). Išvados. IL1A -889C>T ir IL6 -174G>C genotipų pasiskirstymas grupėse pagal APOE ε4 ir grupėse pagal AL progresavimo pobūdį reikšmingai nesiskyrė. Reikšmingų IL1A -889C>T ir IL6 -174G>C polimorfizmų sąsajų su AL rizika nei APOE4+, nei APOE4- tiriamiesiems nenustatyta. Mūsų duomenimis, IL1A -889C>T ir IL6 -174G>C polimorfizmų paveldėjimas nesusijęs su spartesniu AL progresavimu.


2016 ◽  
Vol 28 (9) ◽  
pp. 1409-1424 ◽  
Author(s):  
Shanna L. Burke ◽  
Peter Maramaldi ◽  
Tamara Cadet ◽  
Walter Kukull

ABSTRACTBackground:Alzheimer's disease (AD) is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the US, AD is the most common form of dementia in the elderly, affecting 1 in 10 people over the age of 65. Sleep disturbance has been called a “public health epidemic” and, like depression, is a prodromal symptom of AD but may also contribute to the risk of developing AD. It was hypothesized that sleep disturbance, depression, and the apolipoprotein E (APOE) genotype increase the likelihood of AD.Methods:Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively asymptomatic participants was analyzed. Survival analysis was used to explore the independent relationships between depression, sleep disturbance, and APOE genotypes with eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes.Results:This study reinforced the association between APOE and AD. The hazard of developing AD was eight times higher for those with recent depression and the Ɛ4 homozygote (HR = 8.15 [3.70–17.95]). Among Ɛ4 carriers with clinician-verified depression, the hazard was ten times that of the reference group (HR = 10.11 [4.43–23.09]). The hazard for Ɛ4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR = 6.79 [2.38–19.37]).Conclusion:Findings suggest that sleep disturbance, depression, and APOE Ɛ4 genotype are associated with AD during follow-up evaluations among a group of initially cognitively asymptomatic participants. This study contributes to the literature base exploring an increased hazard or risk of AD due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.


2011 ◽  
Vol 63 (1) ◽  
pp. 89-98 ◽  
Author(s):  
I. Djan ◽  
Edita Stokic ◽  
D. Sakac ◽  
Mihajla Djan ◽  
Dragana Obreht ◽  
...  

Apolipoprotein E displays polymorphism with three common alleles, e2, e3, and e4. The aim of this research was to determine apoE gene polymorphism in a group of healthy patients and a group of patients with CHD, and to reveal the relation between anthropometric and biochemical parameters and the apoE genotype. In CHD group significantly higher values of blood pressure, waist circumference, BMI and fat %, triglycerides, insulin (HOMA IR) and CRP were found. A statistically significant higher presence of the e3e4 genotype and e4 allele was detected in the CHD group. Statistically significant differences between waist circumference, BMI, insulin and HOMA IR were found between subjects with e3e3 and e3e4 genotypes.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S622
Author(s):  
Stefano Monti ◽  
Stefano Monti ◽  
Paola Sebastiani ◽  
Anastasia Gurinovich ◽  
Toshiko Tanaka ◽  
...  

Abstract The discovery of treatments to prevent or delay Alzheimer’s disease is a priority. The gene APOE is associated with cognitive change and late onset Alzheimer’s disease, and epidemiological studies have shown that the e_2 allele of APOE has a neuroprotective effect, and it is associated with increased longevity. We correlated APOE genotype data of 222 New England Centenarian Study participants, including 79 centenarians, 84 centenarian offspring and 55 carriers of APOE e_2, with aptamer-based serum proteomics (SomaLogic technology) of 4783 human proteins corresponding to 4137 genes. We discovered a signature of 16 proteins that associated with different APOE genotypes, and replicated the signature in 3 independent studies. We show that the protein signature tracks with gene expression profiles in brains of late onset Alzheimer’s disease vs. healthy controls. Finally, we show that seven of these proteins correlate with cognitive function changes. Therefore, targeting APOE e_2 molecularly may preserve cognitive function.


2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Francesco Panza ◽  
Davide Seripa ◽  
Grazia D'Onofrio ◽  
Vincenza Frisardi ◽  
Vincenzo Solfrizzi ◽  
...  

Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies.


2020 ◽  
Author(s):  
Lulu Kong ◽  
Yinting Gao ◽  
Wei Li ◽  
Bimin Shi

Abstract Objective To analyze and study the relationship between ApoE gene polymorphism and cardio-cerebrovascular complications in type 2 diabetes mellitus(T2DM) in the Chinese Population. Methods From January 2018 to January 2019, 1140 patients with type 2 diabetes admitted to the Department of Endocrinology, the Affiliated Hospital of Xuzhou Medical University were selected as the case group, including 590 patients with coronary heart disease(CHD) and 550 patients with cerebral infarction(CI), and 1198 patients with type 2 diabetes without complications during the same period were selected as the control group. General baseline data of the two groups were collected, such as gender, age, course of disease, lipid profile, HbA1C, BMI, blood pressure, carotid plaque and complications. ApoE genotypes were identified in all participants who participated in the study. Results This study showed that the ApoE genotypes in both the case group and the control group had the highest frequency of E3/E3. The E3/E4 genotype frequency and E4 allele frequency in the case group were higher than those in the control group (P < 0.05). In the case group, the frequency of E2/E3 and E3/E4 genotypes of CI group was lower than that of CHD group, while the frequency of E3/E3 genotype was higher than that of CHD group. TC and LDL-c levels were significantly increased in patients with ApoE E3/E4 genotype(P < 0.05). ApoE genotype E3/E4 was more associated with carotid plaque than E2/E3. ApoE genotype and ApoE allele were positively correlated with TC and LDL-c levels (P < 0.05).Logistic regression results show that ApoE gene polymorphism is associated with cardio-cerebrovascular complications in T2DM patients. ApoE E3/E4 genotype and allele E4 may be risk factors for T2DM patients with cardio-cerebrovascular complications. Conclusion ApoE E3/E4 genotypes and T2DM patients carrying E4 allele have a higher risk of cardio-cerebrovascular complications than other genotypes. E4 allele may be a risk factor for cardio-cerebrovascular complications in T2DM patients, and its mechanism may be related to the effect of ApoE gene on lipid metabolism.


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