Associations between APOE polymorphisms and seven diseases with cognitive impairment including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies in southeast China

Chen, Keliang; Sun, Yi‐Min; Zhou, Yan; Zhao, Qianhua; Ding, Ding; Guo, Qihao

doi:10.1097/ypg.0000000000000126

Cited by 24 publications

(19 citation statements)

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“…Our results differ from those of other studies presenting a 12-fold [42] or even an 18.6-fold higher odds as previously presented in the Greek population [25]. The presence of APOE ε4 was not related to an increased MCI odds (Table 4) in our study as well as in [43], despite the wealth of data reporting exactly the opposite [11,32,44]. These differences could stem from ethnicity differences, the variation in study design, and the fact that MCI is an etiologically heterogeneous syndrome.…”

Section: Discussioncontrasting

confidence: 57%

“…Only a few studies have been conducted and yet with small sample sizes as presented in Table 6, except for one which has a size comparable to the one used herein [32]. In our study, ε4/4 was 1.6%, ε4/-was 24.1%, and the incidence of ε4 was 13.6%.…”

Section: Discussionmentioning

confidence: 76%

“…On the other hand, the ε3/2 genotype had a protective profile by decreasing the odds for AD by 71.0 and 61.0% for men and women respectively ( Table 5). The investigation of the APOE effect stratified by gender presents controversial results in literature: some studies present men to have a higher AD risk [32,45], while others are at the expense of the above statement, finding women at greater risk than men [46,47]. According to literature, although men may have a higher risk of MCI [48], women are disproportionally affected with AD.…”

Section: Discussionmentioning

confidence: 97%

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Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

et al. 2018

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Background: Apolipoprotein E ε4 allele (APOEε4) is a major genetic risk factor for Alzheimer’s disease (AD). APOEε4 carriers have a higher risk of cognitive impairment and AD in a gene dose-dependent manner. The above notion is investigated in the Greek population. Methods: A sample of 1,703 subjects (967 AD patients, 576 mild cognitive impairment [MCI] and 160 Healthy Elderly), was genotyped for APOE from 2008 to 2017. DNA was extracted from peripheral blood using the QIAamp Blood DNA purification kit (Qiagen Inc., USA). Descriptive statistics, one-way analysis of variance with Bonferroni post hoc tests, Pearson chi-square test, and binary logistic regression models were used for the statistical analysis. Results: The APOE genotype and allele frequencies in AD group were significantly different from those in the Control and MCI groups. The frequencies of ε4/4 homozygotes were 1.9, 1.6, and 5.7%, while the ε4/– carriers’ distribution was 22.5, 24.1, and 37.4% in the Control, MCI, and AD groups respectively. The estimated odds of ε4/4 for AD was 5.731-fold higher compared to the estimated odds of ε3/3. The interaction between gender and APOE did not have a significant effect on the odds for MCI (p = 0.942) and AD (p = 0.984). Conclusion: In Greece, APOE ε4 presence is related to an increased risk for AD in a dose-related manner. Contrary to long-standing views, men and women with the APOE ε4 genotype have nearly the same odds of developing MCI and AD.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 97%

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Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

et al. 2018

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“…The APOE variants, especially its ε4 allele, are the most studied among all genetic variants in people with LBD . Apolipoprotein E (APOE) is involved in cholesterol mobilisation and redistribution during neuronal growth and injury, and it may promote β‐amyloid aggregation .…”

Section: Resultsmentioning

confidence: 99%

“…NOS2 generates nitric oxide in neurons and microglia, and it promotes cell survival though inhibition of apoptosis . Less NOS2 CCTTT repeats lead to reduced level of nitric acid synthase that may increase oxidative stress and may impair neuronal survival in LBD . ESR1 encodes oestrogen receptor alpha (ERα) that mediates the physiological effects of estradiol‐17‐β including neuroprotective and antiapoptotic effects, especially survival of cholinergic neurons, modulating APP processing, and maintaining synaptic density .…”

Section: Discussionmentioning

confidence: 99%

Systematic review of genetic association studies in people with Lewy body dementia

Sanghvi

Singh

Morrin

et al. 2020

Int J Geriat Psychiatry

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Objectives Lewy body dementia (LBD) causes more morbidity, disability, and earlier mortality than Alzheimer disease. Molecular mechanisms underlying neurodegeneration in LBD are poorly understood. We aimed to do a systematic review of all genetic association studies that investigated people with LBD for improving our understanding of LBD molecular genetics and for facilitating discovery of novel biomarkers and therapeutic targets for LBD. Methods We systematically reviewed five online databases (PROSPERO protocol: CRD42018087114) and completed the quality assessment using the quality of genetic association studies tool. Results Eight thousand five hundred twenty‐one articles were screened, and 75 articles were eligible to be included. Genetic associations of LBD with APOE, GBA, and SNCA variants have been replicated by two or more good quality studies. Our meta‐analyses confirmed that APOE‐ε4 is significantly associated with dementia with Lewy bodies (pooled odds ratio [POR] = 2.70; 95% CI, 2.37‐3.07; P < .001) and Parkinson's disease dementia (POR = 1.60; 95% CI, 1.21‐2.11; P = .001). Other reported genetic associations that need further replication include variants in A2M, BCHE‐K, BCL7C, CHRFAM7A, CNTN1, ESR1, GABRB3, MAPT, mitochondrial DNA (mtDNA) haplogroup H, NOS2A, PSEN1, SCARB2, TFAM, TREM2, and UCHL1. Conclusions The reported genetic associations and their potential interactions indicate the importance of α‐synuclein, amyloid, and tau pathology, autophagy lysosomal pathway, ubiquitin proteasome system, oxidative stress, and mitochondrial dysfunction in LBD. There is a need for larger genome‐wide association study (GWAS) for identifying more LBD‐associated genes. Future hypothesis‐driven studies should aim to replicate reported genetic associations of LBD and to explore their functional implications.

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Involvement of ApoE4 in dementia with Lewy bodies in the prodromal and demented stages: evaluation of the Strasbourg cohort

Bousiges,

Cretin,

Muller

et al. 2023

GeroScience

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Background: ApoE4 as a risk factor for AD is no longer a matter of debate. However, it is still an issue for dementia with Lewy bodies (DLB). We wanted to determine the involvement of ApoE4 according to different clinical parameters in our cohort of patients from Strasbourg. Methods: ApoE genotyping was performed on the AlphaLewyMA cohort. In this cohort, 197 patients were genotyped. Among them 105 DLB patients, 37 Alzheimer's disease (AD), 29 comorbidity AD/DLB and 26 control subjects (CS). These groups are also classi ed according to the stage of evolution of the disease: prodromal or demented. We analyzed other parameters in relation to ApoE4, such as socio-educational levels (SEL) and Alzheimer CSF biomarkers (t-Tau, P-Tau, Aβ-42 and Aβ40).Results: There were signi cantly more ApoE4 carriers in the AD (51.4%) and AD/DLB (72.4%) groups compared to the DLB (25.7%) and CS (11.5%) groups (P<0.0001). No signi cant difference was found between the percentage of ApoE4 in the DLB and CS groups, idem between AD and AD/DLB groups. For AD group, we nd a correlation between the age of onset of the disease and the SEL. For DLB group, the correlation does not reach signi cance despite a strong trend (p = 0.056). Interestingly, in this latter group, taking the median of SEL (Education=11 years, i.e. one year before bachelor), the group of patients with high SEL (≥ 11) has signi cantly more patients with ApoE4 than the group of patients with low SEL (<11). Finally, the AD biomarkers do not seem to be impacted by the presence of ApoE4, except for Aβ42. DLB ApoE4 demented patients show a more marked decrease of CSF Aβ42.Conclusions: ApoE4 does not appear to be a risk factor for "pure" DLB patients with the possible exception of patients with high SEL. In the DLB group, ApoE4 would be responsible for the Aβ42 decrease between the prodromal and demented group, suggesting a strong link between ApoE4 and amyloidopathy thus con rming its strong link with AD.Trial registration: ClinicalTrials.gov, (AlphaLewyMa, Identi er: NCT01876459) Regarding genetic risk factors, however, AD and DLB are relatively different. AD and DLB are the subject of numerous GWAS studies, revealing many risk factors in AD such as TREM2, PICALM, BIN1, CLU, CR1, SORL1, CD33 and others (5, 6) some of which are even correlated with Alzheimer biomarkers (7), but different risk factor for DLB: SNCA, GRN, LRP10, SNCB, LRRK2, .Of all these genetic risk factors that have been identi ed for AD, apolipoprotein E4 (ApoE4) appears to be the most important (12, 13). For DLB, there is a substantial literature suggesting that ApoE4 may also be a risk factor including autopsy studies (14-16) and GWAS (9-11, 17). However, recent neuropathologic studies question this and state that this risk factor is only associated with DLB when there is a huge AD comorbidity (18-22), calling into question the direct impact of ApoE4 on synucleinopathy (studies agreeing that ApoE4 is not a risk factor for PD, e.g. ( 14)). In the past, some clinical studies have also questioned ApoE4 as a risk...

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Associations between APOE polymorphisms and seven diseases with cognitive impairment including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies in southeast China

Abstract: Supplemental Digital Content is available in the text.

Cited by 24 publications

References 59 publications

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

Prevalence of Apolipoprotein E Polymorphisms in Alzheimer’s Disease, Mild Cognitive Impairment, and Healthy Elderly: A Northern Greece Study

Systematic review of genetic association studies in people with Lewy body dementia

Involvement of ApoE4 in dementia with Lewy bodies in the prodromal and demented stages: evaluation of the Strasbourg cohort

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