The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2

Suri, Sana; Heise, Verena; Trachtenberg, Aaron J.; Mackay, Clare E.

doi:10.1016/j.neubiorev.2013.10.010

Cited by 160 publications

(161 citation statements)

References 122 publications

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Section: Discussionmentioning

confidence: 99%

“…The e2 carriers were less likely to develop clinical dementia 15,16 and had greater cognitive reserve, 17 since APOE e2 may be neuroprotective. 17 However, e2 carriers also had more cortical amyloid plaques, 18 with elevated risks of cerebral amyloid angiopathy 17 and cortical infarctions. 2 Furthermore, children carrying e2 performed worse on visuospatial tasks 12 and had thicker temporal cortices 5 than non-e2 carriers, similar to adults carrying e2 with mild cognitive impairment or AD.…”

Section: Discussionmentioning

confidence: 99%

“…16 The relative preservation of cognition in aging e2e2 individuals may be due to ApoE e2's antioxidant, anti-inflammatory, and antiproteolytic effects. 17 However, these processes may not be relevant in the developing brain.…”

Section: Figurementioning

confidence: 99%

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Gray matter maturation and cognition in children with different APOE ε genotypes

et al. 2016

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Objective: The aims of the current study were to determine whether children with the 6 different APOE e genotypes show differences in gray matter maturation, particularly for those with e4 and e2 alleles, which are associated with poorer outcomes in many neurologic disorders.Methods: A total of 1,187 healthy children (aged 3-20 years, 52.1% boys, 47.9% girls) with acceptable data from the cross-sectional Pediatric Imaging Neurocognition and Genetics Study were evaluated for the effects of 6 APOE e genotypes on macroscopic and microscopic cortical and subcortical gray matter structures (measured with 3-tesla MRI and FreeSurfer for automated morphometry) and on cognition (NIH Toolbox).Results: Among APOE e4 carriers, age-related changes in brain structures and cognition varied depending on genotype, with the smallest hippocampi in e2e4 children, the lowest hippocampal fractional anisotropy in younger e4e4 children, the largest medial orbitofrontal cortical areas in e3e4 children, and age-dependent thinning of the entorhinal cortex in e4e4 children. Younger e4e4 children had the lowest scores on executive function and working memory, while younger e2e4 children performed worse on attention tasks. Larger parietal gyri in the younger e2e4 children, and thinner temporal and cingulate isthmus cortices or smaller hippocampi in the younger e4e4 children, predicted poorer performance on attention or working memory.Conclusions: Our findings validated and extended prior smaller studies that showed altered brain development in APOE e4-carrier children. The e4e4 and e2e4 genotypes may negatively influence brain development and brain aging at the extremes of age. Studying APOE e polymorphisms in young children may provide the earliest indicators for individuals who might benefit from early interventions or preventive measures for future brain injuries and dementia. Neurology ® 2016;87:585-594 GLOSSARY AD 5 Alzheimer disease; FA 5 fractional anisotropy; GAF 5 genetic ancestry factor; GAM 5 general additive model; PING 5 Pediatric Imaging, Neurocognition, and Genetics; ROI 5 region of interest; SES 5 socioeconomic status; WM 5 working memory.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gray matter maturation and cognition in children with different APOE ε genotypes

et al. 2016

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“…According to the presence or absence of the ɛ4 allele, participants were classified as APOE4 carriers or noncarriers (Table 1). The investigation did not include ɛ2 carriers due to its relatively selective role acting as a protective factor [37, 38] and since its prevalence in the population is low, we did not have a sufficient number of participants in our sample to form a group comparable to the groups of carriers and noncarriers of the ɛ4 allele. Demographic and relevant variables of APOE4 carriers and noncarriers are shown in Table 2.…”

Section: Methodsmentioning

confidence: 99%

<b><i>APOE</i></b> ε4 Genotype and Cognitive Reserve Effects on the Cognitive Functioning of Healthy Elders

López

Turrero

Delgado

et al. 2017

Dement Geriatr Cogn Disord

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Aim: To test the association between cognitive performance and APOE genotype, and to assess potential modifications of this association by sociodemographic and neuroanatomical factors in a sample of 74 healthy elders. Methods: Firstly, we explored the isolated role of the APOE ɛ4 genotype (i.e., APOE4) in different neuropsychological tests, and then the effects of its interaction with sociodemographic (i.e., age, gender, and educational level) and neuroanatomical (i.e., hippocampal volumes) variables. Subsequently, we performed the same analyses after dividing the sample into two subgroups according to their Mini-Mental State Examination scores (control-high group ≥29 and control-low group < 29). Results: In the whole group, APOE4 carriers exhibited a significantly poorer execution in several cognitive domains including global cognitive functioning, episodic memory, verbal fluency, and naming. This effect was more noticeable in older and less educated subjects. The separated analyses revealed that APOE4 carriers in the control-low group exhibited lower scores in global cognitive functioning and episodic memory, while no effects were observed in the control-high group. Neither gender nor hippocampal volumes showed a significant interaction effect with APOE genotype. Conclusions: Current results point out that APOE4 genotype influences healthy aged cognition, although factors such age or educational attainment seem to modulate its effects.

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“…The carriage of the APOE 4 allele has been related to an increased glial activation, oxidative stress, or neuronal injury [21], which could result in altered brain repair mechanisms and a less effective neural protection [22]. Furthermore, ApoE 3 is the normal and most common isoform among the population, and ApoE 2 has been linked to protection against AD and has been also suggested to have a positive influence on cognitive health [23].…”

Section: Introductionmentioning

confidence: 99%

APOE ε4 Modulation of Training Outcomes in Several Cognitive Domains in a Sample of Cognitively Intact Older Adults

López-Higes

Rodríguez-Rojo

Prados

et al. 2017

JAD

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Abstract.Background: Most research points to the 4 allele of the apolipoprotein E (APOE) gene as the most recognizable genetic risk factor associated with Alzheimer's disease pathogenesis. It has been also suggested that the APOE 4 allele has a negative influence on cognitive functioning, which begins long before cognitive impairment becomes manifest. However, still, little is known about the APOE 4 interaction with cognitive intervention programs. Objective: The main goal of this study was to explore whether there was a differential APOE genotype modulation effect after cognitive training in different domains, such as language comprehension, executive functions, and memory. Contrary to other studies, hippocampal volume was controlled for. Methods: Fifty older adults (65+ years; 30 women and 20 men) participated in a multi-domain cognitive training that involved 30 sessions taking place over 12 weeks. Half of the participants were APOE 4 carriers. The control group was matched in age, gender, normalized hippocampal volume, cognitive reserve, Mini-Mental State Examination score, and Geriatric Depression Scale-Short Version. Results: The study revealed that there were consistent treatment benefits in complex sentence comprehension (noncanonical sentences and sentences with two propositions), a domain that was not directly trained, but only in the APOE 4 noncarrier group. Conclusion: Genetic profile modulates training outcomes in sentence comprehension.

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The forgotten APOE allele: A review of the evidence and suggested mechanisms for the protective effect of APOE ɛ2

Cited by 160 publications

References 122 publications

Gray matter maturation and cognition in children with different APOE ε genotypes

Gray matter maturation and cognition in children with different APOE ε genotypes

<b><i>APOE</i></b> ε4 Genotype and Cognitive Reserve Effects on the Cognitive Functioning of Healthy Elders

APOE ε4 Modulation of Training Outcomes in Several Cognitive Domains in a Sample of Cognitively Intact Older Adults

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