scholarly journals Apolipoprotein E genotype and MRI-detected brain alterations pertaining to neurodegeneration: A systematic review

2021 ◽  
Author(s):  
Albert Dayor Piersson ◽  
Mazlyfarina Mohamad ◽  
Subapriya Suppiah ◽  
Nor Fadilah Rajab
Keyword(s):  
Systematic Review ◽  
Apolipoprotein E ◽  
Temporal Lobe ◽  
Late Onset ◽  
Apoe Genotype ◽  
Posterior Cingulate Cortex ◽  
Parahippocampal Gyrus ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Increased Risk

AbstractIntroductionThe effect of apolipoprotein E (APOE) genotype, particularly APOE ε4, the main genetic risk factor for late-onset Alzheimer’s disease (LOAD), has been widely explored in neuroimaging studies pertaining to older adults. The goal of this systematic review was to review the literature on the relationship between carriage of the APOE ε4 allele and grey matter (GM) changes across various age groups and its influence on neurodegeneration as evidenced by structural magnetic resonance imaging (MRI).MethodsA search of the electronic databases Pubmed, Scopus, Ovid and Cochrane was carried out till March 2020. Only studies published in English were included. Risk of bias of each study was assessed using the modified Newcastle-Ottawa Scale.ResultsA total of 115 articles met the inclusion criteria. Methodological quality varied from poor to good. There is moderate evidence of reduced GM volume in the middle frontal gyrus, precuneus, hippocampus, hippocampal subfields, amygdala, parahippocampal gyrus, middle temporal lobe, whole temporal lobe, temporal pole, and posterior cingulate cortex in APOE ε4 carriers.ConclusionThe present data supports the utility of the hippocampal GM volume to evaluate early structural neurodegenerative changes that occurs in APOE ε4 positive elderly individuals who are at increased risk of developing LOAD. Furthermore, the evidence supports serial measurements and comparison of hippocampal volume based on age group, to track the progression of neurodegeneration in APOE ε4 carriers. Additional longitudinal studies are necessary to confirm whether the combination of MRI-detected hippocampal atrophy with APOE ε4 carrier status, can better predict the development of LOAD in cognitively normal individuals.

scholarly journals Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults

2021 ◽  
Vol 11 (1) ◽  
pp. 68
Author(s):  
Sara G. Aguilar-Navarro ◽  
Itzel I. Gonzalez-Aparicio ◽  
José Alberto Avila-Funes ◽  
Teresa Juárez-Cedillo ◽  
Teresa Tusié-Luna ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Cognitive Impairment ◽  
Cardiovascular Risk ◽  
Mild Cognitive Impairment ◽  
Cardiovascular Risk Factors ◽  
Apoe Genotype ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Increased Risk

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

Effect of Apolipoprotein E ɛ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 45 (5-6) ◽  
pp. 335-352 ◽  
Author(s):  
Ying-Chih Cheng ◽  
Yu-Chen Huang ◽  
Hsing-Cheng Liu
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Meta Analysis ◽  
Acetylcholinesterase Inhibitors ◽  
Cognitive Outcomes ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Significant Difference

Background: The apolipoprotein E ɛ4 (APOE ɛ4) genotype is the major genetic risk factor for Alzheimer’s disease (AD). However, its effect on an individual’s response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ɛ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ɛ4 carrier status. Methods: Clinical studies with AD patients reporting APOE ɛ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer’s Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). Results: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ε4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ε4 carriers and APOE ε4 non-carriers (SMD = 0.022, 95% CI: –0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. Conclusions: APOE ɛ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ε4 carrier status.

Apolipoprotein E Genotype and its Effect on Duration and Severity of Early and Late Onset Alzheimer's Disease

1995 ◽  
Vol 167 (4) ◽  
pp. 533-536 ◽  
Author(s):  
Jennie Norrman ◽  
Anthony J. Brookes ◽  
Celia Yates ◽  
David St Clair
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Apoe Genotype ◽  
Increased Risk ◽  
Apolipoprotein E Genotype

BackgroundThe apolipoprotein E (ApoE) ∊4 allele is associated with an increased risk of senile and probably presenile Alzheimer's disease. It is not yet clear whether the ∊4 allele also influences the duration/rate of progress of illness and the severity of the dementia.MethodWe have retrospectively examined a series of ApoE genotyped presenile and senile autopsy cases of Alzheimer's disease (AD) for length of illness and severity of pathology.ResultsWe find no evidence that ApoE genotype affects the rate of progress of AD, but the degree of pathology at death may be increased.ConclusionIt appears that the rate of progress of AD as a whole is independent of the ApoE genotype.

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

2018 ◽  
Vol 18 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Anthoula C. Tsolaki ◽  
Olympia Gatzima ◽  
Makrina Daniilidou ◽  
Eutuxia Lazarou ◽  
Panagiotis D. Bamidis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Dependent Manner ◽  
Apoe Ε4 ◽  
Healthy Elderly ◽  
Increased Risk

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.

scholarly journals Influence of brain-derived neurotrophic factor and apolipoprotein E genetic variants on hemispheric and lateral ventricular volume of young healthy adults

2011 ◽  
Vol 23 (3) ◽  
pp. 132-138 ◽  
Author(s):  
Christos Sidiropoulos ◽  
Kourosh Jafari-Khouzani ◽  
Hamid Soltanian-Zadeh ◽  
Panayiotis Mitsias ◽  
Panagiotis Alexopoulos ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Neurotrophic Factor ◽  
Late Onset ◽  
Apoe Genotype ◽  
Ventricular Volume ◽  
Brain Derived Neurotrophic Factor ◽  
Healthy Adults ◽  
Ventricular Volumes ◽  
Neuronal Processes ◽  
Apoe Genotypes

Objective: Brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) are thought to be implicated in a variety of neuronal processes, including cell growth, resilience to noxious stimuli and synaptic plasticity. A Val to Met substitution at codon 66 in the BDNF protein has been associated with a variety of neuropsychiatric conditions. The ApoE4 allele is considered a risk factor for late-onset Alzheimer's disease, but its effects on young adults are less clear. We sought to investigate the effects of those two polymorphisms on hemispheric and lateral ventricular volumes of young healthy adults.Methods: Hemispheric and lateral ventricular volumes of 144 healthy individuals, aged 19–35 years, were measured using high resolution magnetic resonance imaging and data were correlated with BDNF and ApoE genotypes.Results: There were no correlations between BDNF or ApoE genotype and hemispheric or lateral ventricular volumes.Conclusion: These findings indicate that it is unlikely that either the BDNF Val66Met or ApoE polymorphisms exert any significant effect on hemispheric or lateral ventricular volume. However, confounding epistatic genetic effects as well as relative insensitivity of the volumetric methods used cannot be ruled out. Further imaging analyses are warranted to better define any genetic influence of the BDNF Val6Met and ApoE polymorphism on brain structure of young healthy adults.

scholarly journals APOE genotype regulates pathology and disease progression in synucleinopathy

2020 ◽  
Vol 12 (529) ◽  
pp. eaay3069 ◽  
Author(s):  
Albert A. Davis ◽  
Casey E. Inman ◽  
Zachary M. Wargel ◽  
Umber Dube ◽  
Brittany M. Freeberg ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Transgenic Mice ◽  
Cognitive Decline ◽  
Apolipoprotein E ◽  
Motor Performance ◽  
Apoe Genotype ◽  
Amyloid Β ◽  
Tau Pathology ◽  
Increased Risk ◽  
Over Time

Apolipoprotein E (APOE) ε4 genotype is associated with increased risk of dementia in Parkinson’s disease (PD), but the mechanism is not clear, because patients often have a mixture of α-synuclein (αSyn), amyloid-β (Aβ), and tau pathologies. APOE ε4 exacerbates brain Aβ pathology, as well as tau pathology, but it is not clear whether APOE genotype independently regulates αSyn pathology. In this study, we generated A53T αSyn transgenic mice (A53T) on Apoe knockout (A53T/EKO) or human APOE knockin backgrounds (A53T/E2, E3, and E4). At 12 months of age, A53T/E4 mice accumulated higher amounts of brainstem detergent-insoluble phosphorylated αSyn compared to A53T/EKO and A53T/E3; detergent-insoluble αSyn in A53T/E2 mice was undetectable. By immunohistochemistry, A53T/E4 mice displayed a higher burden of phosphorylated αSyn and reactive gliosis compared to A53T/E2 mice. A53T/E2 mice exhibited increased survival and improved motor performance compared to other APOE genotypes. In a complementary model of αSyn spreading, striatal injection of αSyn preformed fibrils induced greater accumulation of αSyn pathology in the substantia nigra of A53T/E4 mice compared to A53T/E2 and A53T/EKO mice. In two separate cohorts of human patients with PD, APOE ε4/ε4 individuals showed the fastest rate of cognitive decline over time. Our results demonstrate that APOE genotype directly regulates αSyn pathology independent of its established effects on Aβ and tau, corroborate the finding that APOE ε4 exacerbates pathology, and suggest that APOE ε2 may protect against αSyn aggregation and neurodegeneration in synucleinopathies.

scholarly journals Neurodegenerative Disease Risk in Carriers of Autosomal Recessive Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Sophia R. L. Vieira ◽  
Huw R. Morris
Keyword(s):  
Genetic Risk ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Disease Risk ◽  
Late Onset ◽  
Gene Mutations ◽  
Carrier Status ◽  
Lysosomal Storage ◽  
Increased Risk ◽  
Distinct Allele

Genetics has driven significant discoveries in the field of neurodegenerative diseases (NDDs). An emerging theme in neurodegeneration warrants an urgent and comprehensive update: that carrier status of early-onset autosomal recessive (AR) disease, typically considered benign, is associated with an increased risk of a spectrum of late-onset NDDs. Glucosylceramidase beta (GBA1) gene mutations, responsible for the AR lysosomal storage disorder Gaucher disease, are a prominent example of this principle, having been identified as an important genetic risk factor for Parkinson disease. Genetic analyses have revealed further examples, notably GRN, TREM2, EIF2AK3, and several other LSD and mitochondria function genes. In this Review, we discuss the evidence supporting the strikingly distinct allele-dependent clinical phenotypes observed in carriers of such gene mutations and its impact on the wider field of neurodegeneration.

scholarly journals The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amin Gharbi-Meliani ◽  
Aline Dugravot ◽  
Séverine Sabia ◽  
Melina Regy ◽  
Aurore Fayosse ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Life Course ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Adult Life ◽  
Pleiotropic Effect ◽  
Drop Out ◽  
Cognitive Tests ◽  
Increased Risk

Abstract Background Approximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOE ε4), the strongest genetic risk factor for late onset Alzheimer’s disease. Beyond its association with late-onset dementia, the association between APOE ε4 and change in cognition over the adult life course remains uncertain. This study aims to examine whether the association between Apolipoprotein E (APOE) ε4 zygosity and cognition function is modified between midlife and old age. Methods A cohort study of 5561 participants (mean age 55.5 (SD = 5.9) years, 27.1% women) with APOE genotyping and repeated cognitive tests for reasoning, memory, and semantic and phonemic fluency, during a mean (SD) follow-up of 20.2 (2.8) years (the Whitehall II study). We used joint models to examine the association of APOE genotype with cognitive function trajectories between 45 and 85 years taking drop-out, dementia, and death into account and Fine and Gray models to examine associations with dementia. Results Compared to non-carriers, heterozygote (prevalence 25%) and homozygote (prevalence 2%) APOE ε4 carriers had increased risk of dementia, sub-distribution hazard ratios 2.19 (95% CI 1.73, 2.77) and 5.97 (95% CI 3.85, 9.28) respectively. Using data spanning 45–85 years with non-ε4 carriers as the reference, ε4 homozygotes had poorer global cognitive score starting from 65 years; ε4 heterozygotes had better scores between 45 and 55 years, then no difference until poorer cognitive scores from 75 years onwards. In analysis of individual cognitive tests, better cognitive performance in the younger ε4 heterozygotes was primarily attributable to executive function. Conclusions Both heterozygous and homozygous ε4 carriers had poorer cognition and greater risk of dementia at older ages. Our findings show some support for a complex antagonist pleiotropic effect of APOE ε4 heterozygosity over the adult life course, characterized by cognitive advantage in midlife.

Apolipoprotein E ε4/4 genotype limits response to dietary induction of hyperhomocysteinemia and resulting inflammatory signaling

2022 ◽  
pp. 0271678X2110690
Author(s):  
Charles E Seaks ◽  
Erica M Weekman ◽  
Tiffany L Sudduth ◽  
Kevin Xie ◽  
Brandi Wasek ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Apoe Ε4 ◽  
Perivascular Inflammation ◽  
Ε4 Allele ◽  
Barrier Breakdown ◽  
The Impact

Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind Alzheimer’s disease. Apolipoprotein E (ApoE) is a lipid transporting lipoprotein found within the brain and periphery. The APOE ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease and is a risk factor for VCID. Our lab has previously utilized a dietary model of hyperhomocysteinemia (HHcy) to induce VCID pathology and cognitive deficits in mice. This diet induces perivascular inflammation through cumulative oxidative damage leading to glial mediated inflammation and blood brain barrier breakdown. Here, we examine the impact of ApoE ε4 compared to ε3 alleles on the progression of VCID pathology and inflammation in our dietary model of HHcy. We report a significant resistance to HHcy induction in ε4 mice, accompanied by a number of related differences related to homocysteine (Hcy) metabolism and methylation cycle, or 1-C, metabolites. There were also significant differences in inflammatory profiles between ε3 and ε4 mice, as well as significant reduction in Serpina3n, a serine protease inhibitor associated with ApoE ε4, expression in ε4 HHcy mice relative to ε4 controls. Finally, we find evidence of pervasive sex differences within both genotypes in response to HHcy induction.

scholarly journals Apolipoprotein E and Functional Illness in the Elderly

1998 ◽  
Vol 10 (1) ◽  
pp. 3-6
Author(s):  
Clive Holmes
Keyword(s):  
Risk Factor ◽  
Protective Factors ◽  
Apolipoprotein E ◽  
Age Of Onset ◽  
Late Onset ◽  
The Elderly ◽  
Protective Role ◽  
Depressive Illness ◽  
Apoe Ε4 ◽  
Psychiatric Conditions

Following on from the hypothesis of a role for the ApoE ε4 and ε2 alleles as risk and protective factors, respectively, for late-onset Alzheimer's disease (AD) came inevitable questions regarding other psychiatric conditions of late onset including depressive illness and schizophrenia. Is ApoE ε4 a risk factor in these diseases and do carriers have an earlier age of onset? Does ApoE ε2 have a protective role, with carriers of this allele having a later age of onset?

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