The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease

Trachtenberg, Aaron J.; Filippini, Nicola; Cheeseman, Jane; Duff, Eugene P.; Neville, Matt J.; Ebmeier, Klaus P.; Karpe, Fredrik; Mackay, Clare E.

doi:10.1016/j.neurobiolaging.2010.11.011

Cited by 51 publications

(56 citation statements)

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“…Research probing the relationship between APOE e4 and amyloid across the lifespan found that despite no episodic memory performance difference, e4 carriers showed accelerated deposition of amyloid, with 10% of the population defined as amyloid positive by halfway through the fifth decade (Jack et al, 2015). This may also be the route by which APOE e4 impacts functional connectivity (Sheline et al, 2010), demonstrated in the earlier research of Trachtenberg et al (2012a;2012b). These changes may be particularly relevant for executive attention, which requires communication between multiple processing regions.…”

Section: Discussionmentioning

confidence: 89%

“…In light of the opposing effects of APOE variants on dementia risk, intuitively differences are expected in the cognitive profile of e4 and e2 carriers. Recent research, however, has found overlapping patterns of task-related functional activity in mid-age e2 and e4 carriers, compared to an e3 group, during both a Stroop task, and an episodic memory task (Trachtenberg et al, 2012a). Both genotype groups also showed differences in resting-state activity compared to an e3 group (Trachtenberg et al, 2012b).…”

Section: Introductionmentioning

confidence: 88%

“…In light of recent research (Trachtenberg et al, 2012a;Trachtenberg et al, 2012b), it is unclear whether e2 carriers will show equal or advantaged performance compared to homozygous e3 carriers. This study took an exploratory look at the e2 effects on attentional control mechanisms, to provide the foundation for future work establishing the profile of this genotype in midadulthood.…”

Section: Introductionmentioning

confidence: 99%

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The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Lancaster

Tabet

Rusted

2016

Neurobiology of Aging

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Article (Accepted Version) http://sro.sussex.ac.uk Lancaster, Claire, Tabet, Naji and Rusted, Jennifer (2016) The APOE paradox: how do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline. Neurobiology of Aging, This version is available from Sussex Research Online: http://sro.sussex.ac.uk/62415/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. AbstractPossession of an APOE e4 allele is an established risk factor for Alzheimer's disease, while the less commonly studied e2 variant is premised to offer some protection. This research explores the purported deleterious-protective dichotomy of APOE variants on attentional control in mid-adulthood. 66 volunteers, aged 45-55 years, completed three tasks that provided complementary measures of attentional control: prospective memory, sustained attention and inhibition. Performance was compared between e2 carriers, e4 carriers and e3 homozygotes (the population norm). Carriers of the e4 allele showed subtle disadvantages, compared to the e3 group, in accuracy of Stroop task and prospective memory performance. Contrary to expectations, e2 carriers showed performance disadvantages in sustained attention. The finding of detrimental effects in attentional control for both e4 and e2 complicates the current model that proposes opposing effects of these variants on later-life cognition. Future research is needed to understand how cognitive differences develop with increasing age, and the physiological mechanisms that underpin these changes.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Lancaster

Tabet

Rusted

2016

Neurobiology of Aging

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“…95,114,115 Although e4-related hypometabolism has been associated with the neuropathological processes of AD, 112,116 such findings may not be necessarily pathological or specifically linked to AD. 117 For instance, APOE e4 is also a risk factor for vascular disease. 118 Moreover, a study that used both FDG-PET and amyloid imaging to assess cognitively normal older adults showed that cerebral hypometabolism associated with e4 is not mediated by amyloid deposition.…”

Section: Cardiovascular Risk Factors and Cognitive Declinementioning

confidence: 99%

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

Ferreira

Tamashiro-Duran

Squarzoni

et al. 2014

Rev. Bras. Psiquiatr.

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Objective: To review functional neuroimaging studies about the relationship between cardiovascular risk factors (CVRFs), Alzheimer's disease (AD), and mild cognitive impairment (MCI). Methods: We performed a comprehensive literature search to identify articles in the neuroimaging field addressing CVRF in AD and MCI. We included studies that used positron emission tomography (PET), single photon emission computerized tomography (SPECT), or functional magnetic resonance imaging (fMRI). Results: CVRFs have been considered risk factors for cognitive decline, MCI, and AD. Patterns of AD-like changes in brain function have been found in association with several CVRFs (both regarding individual risk factors and also composite CVRF measures). In vivo assessment of AD-related pathology with amyloid imaging techniques provided further evidence linking CVRFs and AD, but there is still limited information resulting from this new technology. Conclusion: There is a large body of evidence from functional neuroimaging studies supporting the hypothesis that CVRFs may play a causal role in the pathophysiology of AD. A major limitation of most studies is their cross-sectional design; future longitudinal studies using multiple imaging modalities are expected to better document changes in CVRF-related brain function patterns and provide a clearer picture of the complex relationship between aging, CVRFs, and AD.

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“…Los individuos con aparición tardía que portan una o dos copias del alelo APOEε4 desarrollan los síntomas de la enfermedad 10 a 20 años más temprano, comparados con los individuos que no llevan este alelo (15). El alelo APOEε2, menos común tanto en individuos con enfermedad de Alzheimer como en la población general, parece actuar como un factor protector para la aparición de la enfermedad (20,21).…”

Section: Polimorfismos De Apoe En El Síndrome De Downunclassified

Polimorfismos del gen ApoE en individuos con síndrome de Down y sus progenitores en una población colombiana

2012

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Introducción. Los polimorfismos en el gen ApoE se han examinado en el síndrome de Down debido a la relación existente de la isoforma E4 con la demencia de tipo Alzheimer que aparece en los individuos con síndrome de Down. Objetivos. Determinar los polimorfismos en el gen ApoE en individuos con síndrome de Down y sus progenitores, y buscar su asociación. Materiales y métodos. Mediante PCR-RFLP, se analizaron los polimorfismos del gen ApoE en 134 individuos jóvenes con síndrome de Down, 87 madres y 54 padres del eje cafetero, y se compararon con una población control de 525 individuos sanos. Resultados. El alelo APOEε3 y el genotipo ε3/ε3 fueron los más frecuentes en todas las poblaciones. La frecuencia alélica de APOEε2 es muy baja y ε2/ε2 está ausente en las poblaciones con síndrome de Down y sus progenitores. El alelo APOEε4 fue más frecuente en individuos con síndrome de Down que en el resto de poblaciones analizadas. Al comparar las frecuencias alélicas y genotípicas entre las poblaciones con síndrome de Down y los progenitores con la población control, mediante la χ 2 de Pearson y los odds ratios por la prueba exacta de Fisher, no se encontraron diferencias estadísticamente significativas. Conclusiones. No se encontró asociación entre los polimorfismos del gen ApoE y el síndrome de Down. Es posible que el tamaño de la muestra o las influencias étnicas hubieran afectado estos resultados. Es necesario hacer otros estudios en poblaciones colombianas y evaluar la asociación con otros genes que se encuentran relacionados con la enfermedad de Alzheimer.Palabras clave: apolipoproteínas E, síndrome de Down, enfermedad de Alzheimer, alelos, genotipo, Colombia. APOE gene polymorphisms associated with Down syndrome in Colombian populationsIntroduction. Gene APOEε4 allele polymorphisms have been examined in Down syndrome because of the relationship between (a) the E4 isoform and (b) the type of Alzheimer's dementia that appears in individuals with Down syndrome. This isoform is considered a risk factor for Alzheimer´s disease development and has been associated with early death in Down syndrome. Objectives. The polymorphisms in the APOE gene were characterized for Down syndrome individuals and their parents, in order to detect associations between the APOE polymorphisms and Down syndrome. Materials and methods. APOE gene polymorphisms were detected by RFLP-PCR and analyzed in 134 young individuals with Down syndrome, 87 mothers and 54 fathers, residents of the departments of Quindío and Risaralda, Colombia. The controls were 525 healthy individuals. Results. The APOEε3 allele and ε3/ε3 genotype were most frequent in all the populations (83-90% and 70-78%). The allelic frequency of APOEε2 was very low and ε2/ε2 (3-7%) was absent in Down syndrome and their parents. The allele APOEε4 was more frequent (11% vs. 9%) in Down syndrome individuals than in the controls. Comparing the allelic and genotypic frequencies between the populations with Down syndrome and their parents with the controls using Pearson χ 2 test and Fisher'...

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The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease

Cited by 51 publications

References 63 publications

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

The link between cardiovascular risk, Alzheimer's disease, and mild cognitive impairment: support from recent functional neuroimaging studies

Polimorfismos del gen ApoE en individuos con síndrome de Down y sus progenitores en una población colombiana

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