Interaction with the MAPT H1H1 Genotype Increases Dementia Risk in APOE ε4 Carriers in a Population of Southern India

2016 ◽  
Vol 42 (5-6) ◽  
pp. 255-264 ◽  
Author(s):  
P.S. Jairani ◽  
P.M. Aswathy ◽  
Srinivas Gopala ◽  
Joe Verghese ◽  
P.S. Mathuranath
Keyword(s):  
Disease Risk ◽  
Strong Association ◽  
Multivariate Logistic Regression Analysis ◽  
Lewy Bodies ◽  
Southern India ◽  
Control Group ◽  
Apoe Ε4 ◽  
Dementia Patients ◽  
Dementia Risk ◽  
Ε4 Allele

Background: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. Methods: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138). APOE genotyping and MAPT haplotyping were performed on all study subjects. Results: Multivariate logistic regression analysis showed that variability on the APOE locus influenced the relative risk of dementia in the study population. The APOE ε4 allele increased the disease risk most significantly for AD (OR = 3.468, p < 0.0001) and MCI (OR = 2.901, p < 0.0001). The APOE ε2 allele remained protective for AD (OR = 0.205, p < 0.05). For FTD, VD, and DLB, the APOE ε4 allele was ineffectual in modulating disease risk. The MAPT H1 haplotype was not an overrepresented marker of neurodegenerative diseases. The H1H1 genotype had an additive effect in contributing to either disease risk in combination with the APOE ε4 allele or protection in combination with the APOE ε2 or ε3 allele. Conclusions: This study is a reappraisal of the strong association of APOE variability with AD in southern India when compared to other dementia groups, while the transcriptional differences between MAPT haplotypes have a limited role in Indian dementia patients.

APOE ε4 Allele Status in Korean Dementia Patients with Severe White Matter Hyperintensities

2011 ◽  
Vol 24 (3) ◽  
pp. 519-524 ◽  
Author(s):  
Yun Jeong Hong ◽  
Bora Yoon ◽  
Yong S. Shim ◽  
A-Hyun Cho ◽  
Hae-Eun Shin ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Apoe Ε4 ◽  
Dementia Patients ◽  
Allele Status ◽  
Ε4 Allele

P1-338: THE EFFECT OF APOE ε4 ALLELE AND LEWY BODIES ON SLEEP DISTURBANCES ALONG THE SPECTRUM OF ALZHEIMER'S PATHOLOGY LOAD

2006 ◽  
Vol 14 (7S_Part_7) ◽  
pp. P422-P423
Author(s):  
Ka Yi Koo ◽  
Tom A. Schweizer ◽  
Corinne E. Fischer ◽  
David G. Munoz
Keyword(s):  
Sleep Disturbances ◽  
Lewy Bodies ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Alzheimer’S Pathology

scholarly journals Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease

2018 ◽  
Vol 15 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Winnie Qian ◽  
Corinne E. Fischer ◽  
Tom A. Schweizer ◽  
David G. Munoz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apoe Genotype ◽  
Lewy Bodies ◽  
Functional Impairments ◽  
Significant Interaction Effect ◽  
Functional Activities ◽  
Apoe Ε4 ◽  
Lewy Body Pathology ◽  
Ε4 Allele

Background: Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ε4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear. Objective: We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ε4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ε4, Lewy bodies, and psychosis. Methods: Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ε4, as well as their interaction. Results: Psychosis and the presence of APOE ε4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ε4 on MMSE scores, with APOE ε4 negatively affecting patients with hallucinations-only psychosis. APOE ε4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. Conclusion: Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ε4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ε4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.

Inheritance of the ApoE ε4 Allele Increases the Rate of Brain Atrophy in Dementia Patients

1999 ◽  
Vol 10 (4) ◽  
pp. 262-268 ◽  
Author(s):  
Lars-Olof Wahlund ◽  
Per Julin ◽  
Lars Lannfelt ◽  
Johan Lindqvist ◽  
Leif Svensson
Keyword(s):  
Brain Atrophy ◽  
Apoe Ε4 ◽  
Dementia Patients ◽  
Ε4 Allele

scholarly journals Environmental factors influencing the link between APOE ε4 and Alzheimer's disease (AD) risk

2018 ◽  
Vol 31 (2) ◽  
pp. 305-306 ◽  
Author(s):  
Keith Fluegge
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Temporal Relationship ◽  
Disease Risk ◽  
Apoe Ε4 ◽  
Factors Influencing ◽  
Increased Risk ◽  
Ε4 Allele

While APOE ε4 allele is considered a genetic risk factor for Alzheimer's disease (AD), no relation existed between APOE ε4 and AD in the Yoruba in Nigeria among cohorts included in early prevalence waves. The authors’ explanation that other disease susceptibilities may provoke earlier mortality is inconsistent with the Yoruba having a lower incidence of disease risk factors. Cohort enrichment in 2001 has altered the authors’ conclusions; Yorba participants homozygous, and not heterozygous, for the ε4 allele had significantly increased risk for AD (HR = 2.95, p = 0.0002) (Hendrie et al., 2014). This is a critical revelation, yet it is not clear why such a temporal relationship exists between risk genotypes and AD among the Yoruba. This letter proposes an explanation.

scholarly journals Association Study of Apolipoprotein E Gene Polymorphism With Incidence and Delayed Resolution of Hemifacial Spasm

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianxin Zhou ◽  
Li Jiang ◽  
Sangui Yuan ◽  
Jiashang Huang ◽  
Quanhong Shi ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Hemifacial Spasm ◽  
Control Group ◽  
Resolution Rate ◽  
E Gene ◽  
Apoe Ε4 ◽  
Apolipoprotein E Gene ◽  
Significant Difference ◽  
Ε4 Allele ◽  
Hemifacial Spasms

Objective: This study investigates the correlation between Apolipoprotein E gene (APOE) polymorphism and the incidence and delayed resolution of hemifacial spasms.Methods: The APOE genotypes of 151 patients with hemifacial spasm and 73 control cases were determined by cleaved amplification polymorphism sequence-tagged sites. The distribution of three APOE alleles (ε2, ε3, and ε4) in two groups and the delayed resolution rate in 6 genotypes were calculated and statistically analyzed.Results: The proportion of patients with APOE ε3/ε4 genotype in the hemifacial spasm group (25.17%) was significantly higher than that in the control group (12.33%) (P = 0.027). In terms of allele frequency, the proportion of the APOE ε4 allele in the hemifacial spasm group (15.56%) was significantly higher than that in the control group (6.85%) (P = 0.009). Meanwhile, the proportion of APOE ε4 allele carriers in the hemifacial spasm group (29.80%) was significantly higher than that in the control group (13.7%) (P = 0.009). Logistic regression analysis showed that the ε4 allele significantly increased the incidence of hemifacial spasm (OR 2.675, 95%CI 1.260-5.678, P = 0.010). Among the 32 patients with a delayed resolution, the ε3/ε3 and ε3/ε4 had the highest proportion in 6 genotypes. The delayed resolution rate of APOE ε3/ε4 (34.21%) was significantly higher than APOE ε3/ε3 (17.78%) (P &lt; 0.05). The delayed resolution rate of APOE ε4 carriers was the highest (33.33%) in the 3 allele carriers, but there was no significant difference among the 3 allele carriers (P = 0.065).Conclusion: The polymorphism of APOE is relevant to the incidence rate of hemifacial spasms. APOE ε4 allele increases the incidence of hemifacial spasm. The APOE ε4 allele may promote the occurrence of delayed resolution.

scholarly journals OxLDL plasma levels in patients with Alzheimer's disease

2018 ◽  
Vol 76 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Marina Felipe Grossi ◽  
Maria das Graças Carvalho ◽  
Josianne Nicácio Silveira ◽  
Gisele Santos Gonçalves ◽  
Karina Braga Gomes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Control Group ◽  
Apoe Polymorphism ◽  
Elderly Individuals ◽  
Apoe Ε4 ◽  
Group A ◽  
Ε4 Allele ◽  
Polymerase Chain ◽  
Apoe Gene Polymorphism

ABSTRACT Objective: The objective of this study was to characterize the conventional lipid profile, oxLDL levels and ApoE polymorphism in patients with Alzheimer's disease (AD) and in elderly individuals without cognitive impairment. Methods: Eighty elderly individuals were selected and the levels of oxLDL were determined using the ELISA kit, and ApoE gene polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism. Results: Significantly reduced levels of oxLDL were observed in patients with AD compared to the control group. A higher frequency of the ApoE ε4 allele was observed in patients with AD compared to controls. No difference was observed for total cholesterol, HDL-C, and LDL-C levels between the two groups, while triglyceride levels were higher in controls compared with patients with AD. Conclusion: The data analyzed together did not reveal significant differences in lipid profiles, including oxLDL levels. However, the importance of lipid changes in the genesis of the disease cannot be ruled out. Nevertheless, the ApoE ε4 allele was significantly more frequent in patients with Alzheimer's dementia in agreement with previous findings in the literature, but this genetic component did not change the levels of oxLDL.

scholarly journals Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Na Zhang ◽  
Janice M. Ranson ◽  
Zhi-Jie Zheng ◽  
Eilis Hannon ◽  
Zhenwei Zhou ◽  
...  
Keyword(s):  
Genetic Predisposition ◽  
Significant Interaction ◽  
Smoking Status ◽  
Apoe Genotype ◽  
Population Based ◽  
Polygenic Risk ◽  
Apoe Ε4 ◽  
Dementia Risk ◽  
Ε4 Allele ◽  
Never Smokers

AbstractWe evaluated whether the association between cigarette smoking and dementia risk is modified by genetic predisposition including apolipoprotein E (APOE) genotype and polygenic risk (excluding the APOE region). We included 193,198 UK Biobank participants aged 60–73 years without dementia at baseline. Of non-APOE-ε4 carriers, 0.89% (95% CI 0.73–1.08%) current smokers developed dementia compared with 0.49% (95% CI 0.44–0.55%) of never smokers (adjusted HR 1.78; 95% CI 1.39–2.29). In contrast, of one APOE-ε4 allele carriers, 1.69% (95% CI 1.31–2.12%) current smokers developed dementia compared with 1.40% (95% CI 1.25–1.55%) of never smokers (adjusted HR 1.06; 95% CI 0.77–1.45); of two APOE-ε4 alleles carriers, 4.90% (95% CI 2.92–7.61%) current smokers developed dementia compared with 3.87% (95% CI 3.11–4.74%) of never smokers (adjusted HR 0.94; 95% CI 0.49–1.79). Of participants with high polygenic risk, 1.77% (95% CI 1.35–2.27%) current smokers developed dementia compared with 1.05% (95% CI 0.91–1.21%) of never smokers (adjusted HR 1.63; 95% CI 1.16–2.28). A significant interaction was found between APOE genotype and smoking status (P = 0.002) while no significant interaction was identified between polygenic risk and smoking status (P = 0.25). APOE genotype but not polygenic risk modified the effect of smoking on dementia risk.

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