Apolipoprotein E Polymorphism and Dementia: A Hospital-Based Study from Southern India

Bharath, Srikala; Purushottam, Meera; Mukherjee, Odity; Bagepally, Bhavani Shankara; Prakash, Om; Kota, Lakshminarayanan; Krishnappa, Srinivas Brahmadevarahalli; Sivakumar, Palanimuthu T.; Jain, Sanjeev; Varghese, Mathew

doi:10.1159/000322093

Cited by 26 publications

(22 citation statements)

References 51 publications

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“…This was the largest study, comprising 419 patients with dementia and 138 age-matched controls, when compared to the other Indian studies done so far [24,33,34,40]. Regarding the genetic factors analysed in the cohort, a strong positive association was established between the APOE ε4 allele and AD, which is in concordance with previous reports worldwide.…”

Section: Discussionsupporting

confidence: 88%

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

Jairani

Aswathy

Gopala

et al. 2016

Dement Geriatr Cogn Disord

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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.

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Section: Discussionsupporting

confidence: 88%

“…39.42% for the AD group and 17.75% for the controls. These figures are higher than those from the single southern Indian report [24]. It has been reported that amyloid pathology and tau pathology are interlinked, and are quite complementary to one another, leading to neurodegeneration in AD [35].…”

Section: Discussionmentioning

confidence: 76%

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

Jairani

Aswathy

Gopala

et al. 2016

Dement Geriatr Cogn Disord

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“…[30] However, a clinic-based study from South India confirmed the increased frequency of ApoE4 in patients with dementia (0.18), especially among those with AD (0.21), and also in VaD. [31] The frequency was higher than that reported in the other rural community-based study from North India (0.15 in all dementias) and the hospital-based study. A study from Central India has shown positive influence of presenilin gene (PS1, allele 1) and ApoE gene e-4 alleles, increasing the susceptibility for degenerative dementia as compared to VaD.…”

Section: Genetics Of Dementia In Indiamentioning

confidence: 82%

Dementia: Indian scenario

2012

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As per the estimates of the World Health Organization, aging population is increasing in developing countries and dementia is going to become epidemic among elderly in the coming decades. This demands early action to prevent the disease and treatment of the affected persons, which is poorly existent in middle- and low-income countries. The need of the hour to tackle dementia in India is to estimate disease burden in the community, search for risk and protective factors of dementia, and undertake measures to provide social benefits to the sufferers and those who are at risk. Raising awareness among the public and general physicians is an important task ahead. In India, there is lack of good longitudinal studies which can provide true trend of the disease and determine risk factors, paucity of basic and clinical researches on dementia, poor awareness, and inadequate availability of social benefit. India, being a country of diverse ethnicity and cultures, has great advantages to carry out genetic epidemiological study. The information may be useful for undertaking remedial measure. This article will highlight the existing state of the above medical and social issues and deficiencies, so that the stakeholders can make adequate preparation to provide relief to the dementia patients and those who are at risk. It is expected that the medical and scientific community will draw attention to the medical problem with the help of governmental and non-governmental agencies, and the political leadership will be motivated to undertake the issue of providing socioeconomic benefit to families of the victims.

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“…A recent study reported widespread reduction in FA in both young and elderly ApoE 4 carriers without significant differential changes with age [7] . These differences could be due to sample size effects, and geographical and population variability in ApoE 4 frequency [15] . Brain atrophy in AD seems to be influenced by ApoE, and it has been observed that greater 4 load is associated with increased susceptibility of the temporal cortex, amygdala and limbic regions [21,22] .…”

Section: Discussionmentioning

confidence: 99%

“…DTI was acquired in 32 directions at b values of 0 and 1,000 using a Philips Achieva 3-tesla MRI scanner. The subjects who participated in the present study were recruited as part of larger ongoing studies at the clinic [15] .…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein E4 and Brain White Matter Integrity in Alzheimer’s Disease: Tract-Based Spatial Statistics Study under 3-Tesla MRI

et al. 2012

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Introduction: Apolipoprotein E4 (ApoE ε4) polymorphism is a known genetic risk factor for Alzheimer’s disease (AD). Objectives: To evaluate the role of ApoE ε4 on white matter structural integrity in AD. Methods: Subjects were 32 patients with probable AD (ApoE ε4-positive: n = 15) and 18 matched controls (ApoE ε4-positive: n = 6). All subjects were right-handed, evaluated using standard scales and genotyped at the ApoE locus. Diffusion tensor imaging was performed with a 3-tesla MRI scanner and analyzed using the tract-based spatial statistics method. Results: AD patients had significantly lower fractional anisotropy (FA) in bilateral temporoparietal, limbic and parahippocampal regions in comparison to healthy comparison subjects. ApoE ε4 carriers among both AD and healthy comparison subjects showed lower FA in limbic and medial temporal regions. Conclusions: There is a modest association between ApoE ε4 carrier status and reduction in white matter tract integrity at medial temporal and limbic regions in both healthy and AD subjects.

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Apolipoprotein E Polymorphism and Dementia: A Hospital-Based Study from Southern India

Cited by 26 publications

References 51 publications

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

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

Dementia: Indian scenario

Apolipoprotein E4 and Brain White Matter Integrity in Alzheimer’s Disease: Tract-Based Spatial Statistics Study under 3-Tesla MRI

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