Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E ϵ4 allele

Tohgi, Hideo; Takahashi, Satoshi; Kato, E; Homma, Akira; Niina, Rie; Sasaki, Kazuhiro; Yonezawa, Hisashi; Sasaki, Makoto

doi:10.1016/s0304-3940(97)00743-x

Cited by 92 publications

(55 citation statements)

References 22 publications

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“…A tendency towards a greater right-sided medial temporal atrophy was detected with VBM in MCI [15] and in AD [26,[46][47][48] . Hippocampal asymmetry has previously been shown to be dependent on the ApoE genotype already in nondemented subjects [49,50] , with a smaller right hippocampus than the left in subjects homozygous for the 4 allele. A dose-dependent effect of the ApoE 4 allele on asymmetry in MTL regions was shown also in AD [29,51 , for a review see 5] , where the right side appeared more atrophied than the left not only for the hippocampus, but also for the amygdala in 4/4 carriers [51] .…”

Section: Discussionmentioning

confidence: 95%

The Effect of Apolipoprotein Polymorphism on Brain in Mild Cognitive Impairment: A Voxel-Based Morphometric Study

Pennanen

Testa

Boccardi

et al. 2006

Dement Geriatr Cogn Disord

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We investigated the effect of apolipoprotein E (ApoE) on the whole brain in 51 individuals with mild cognitive impairment using voxel-based morphometry. Between cases heterozygous for the ApoE Ε4 (n = 15) and those who were ApoE Ε4 noncarriers (n = 28), only the right parahippocampal gyrus, with the entorhinal cortex included, reached the level of statistical significance. In cases homozygous for the Ε4 allele (n = 8) versus noncarriers, the greatest atrophy was located in the right amygdala followed by the right parahippocampal gyrus, the left amygdala and the left medial dorsal thalamic nucleus.

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Section: Discussionmentioning

confidence: 95%

The Effect of Apolipoprotein Polymorphism on Brain in Mild Cognitive Impairment: A Voxel-Based Morphometric Study

Pennanen

Testa

Boccardi

et al. 2006

Dement Geriatr Cogn Disord

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“…Conversely though, there is also evidence that cognitive performance is not affected by ɛ4 genotype in healthy adulthood (e.g., Bathum et al, 2006;Bunce, Fratiglioni, Small, Winblad, & Backman, 2004;Chen et al, 2002; Garcia et al, 2008;Jacobson et al, 2005;Kim et al, 2002;Marquis et al, 2002; Salo et al, 2001;Tohgi et al, 1997; Ystad et al, 2009), or that older ɛ4 carriers even show better cognitive performance (e.g., Carrion-Baralt et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

APOE ε4 and cognitive function in early life: A meta-analysis.

Ihle¹,

Bunce²,

Kliegel³

2012

Neuropsychology

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Introduction. It is well established that the Apolipoprotein E (APOE) ε4 allele is associated with cognitive impairment and Alzheimer's disease in old age. By contrast, several studies have demonstrated cognitive benefits in young ε4 carriers. It is therefore possible that the ε4 allele exhibits a pleiotropic association with cognition across the lifespan where ε4-related benefits in youth reverse in later life to become risk factors for cognitive impairment and dementia in later life. To date though, there has been no broad quantitative review of work assessing APOE-cognition associations in children, adolescents and young adults.Methods. Based on 20 studies investigating cognitive performance in ε4 carrying young persons and their non-ε4 counterparts, a meta-analytic study was conducted to examine APOE ε 4-related differences in cognitive performance. Additionally, we assessed whether the level of executive demands affected the strength of association between the ε4 allele and cognitive measure.Results. In all analyses, estimated APOE ε4 related population effect sizes did not reliably differ from zero. Furthermore, the level of executive demands of the task did not affect this finding. Conclusion.We found no APOE ε4-related cognitive benefits in young adults, adolescents, and children and findings were not moderated by the level of executive demands in a cognitive task. Given the current empirical evidence therefore, suggestions that APOE ε4 exhibits a pleiotropic association with cognition across the lifespan should be treated with caution.Key words: Apolipoprotein E; APOE; cognition; cognitive performance; executive processes; young adults; adolescence; childhood; meta-analysis 3 Apolipoprotein E (APOE) is a protein that plays an important role in cholesterol transportation (for reviews of the mechanisms and functions of APOE in the nervous system, see Czyzewski, Pfeffer, & Barcikowska, 1998; Harris et al., 2003;Lahiri, Sambamurti, & Bennett, 2004;Mahley, 1988;Menzel, Kladetzky, & Assmann, 1983;Rocchi, Pellegrini, Siciliano, & Murri, 2003;Rubinsztein, 1995). The gene coding for APOE is located on chromosome 19 and has three alleles, ɛ2, ɛ3, and ɛ4.APOE ɛ4 is well established as a risk factor for Alzheimer's disease (AD: Corder et al., 1993; Saunders et al, 1993), where persons possessing the ɛ4 allele have a three to four times higher risk for developing AD (see also Farrer et al., 1997, for a meta-analysis on effects of age, sex, and ethnicity on the association between APOE genotype and AD).Moreover, various studies have found that APOE ɛ4 is strongly associated with cognitive decline among persons who have been diagnosed with AD (e.g., Hirono, Hashimoto, Yasuda, Kazui, & Mori, 2003;Marra et al., 2004;Martins, Oulhaj, De Jager, & Williams, 2005;Plassman & Breitner, 1996). In addition, more than a decade of research has also demonstrated deficits in various cognitive domains in non-demented ɛ4 carriers in comparison with non-ɛ4 carriers in middle and old adulthood (e.g., Berr et al., 1996;Cantu, ...

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“…Thus, several studies have reported a significant atrophy (or cortical thinning) in APOE4 carriers compared to non carriers, most often in brain regions most susceptible to AD, i.e. medial temporal structures (hippocampus, entorhinal cortex, etc;Plassman et al, 1997;Tohgi et al, 1997;Lemaître et al, 2005;Lind et al, 2006;Wishart et al, 2006;Burggren et al, 2008;Honea et al, 2009;Suthana et al, 2010;O'Dwyer et al, 2012). Other regions are also reported such as the lateral temporal and prefrontal cortex (Wishart et al, 2006) or parietal areas (Honea et al, 2009).…”

Section: Apoe4 and Structural Mri / Atrophymentioning

confidence: 99%

Neuroimaging biomarkers for Alzheimer's disease in asymptomatic APOE4 carriers

Chételat

Fouquet

2013

Revue Neurologique

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Abstract:Introduction. The E4 allele of the apolipoprotein E (APOE4) is the major known genetic risk factor for AD, with a dramatic increase in the risk of developing AD as the number of APOE4 alleles increases from 0 to 2. For this reason, asymptomatic APOE4 carriers as a group offer a great opportunity to seek for the presence of early biomarkers for AD. The present article reviews neuroimaging studies on APOE4 carriers, focusing on cognitively normal individuals and on the main neuroimaging biomarkers for AD, i.e. atrophy with structural MRI, hypometabolism with FDG-PET, and amyloid deposition with amyloid-PET imaging.State of art. There is a great number of studies on the effect of APOE4 on brain structures, and they tend to show significant atrophy in APOE4 carriers compared to non carriers especially in regions susceptible to AD pathology such as the hippocampus. However, results are rather discrepant which suggests that the effect of APOE4 on brain structure is subtle. As for FDG-PET metabolism, the few studies show decreased metabolism, again especially in AD-sensitive regions such as posterior associative parietal areas, with a dose-dependent effect (i.e. worsening as the number of APOE4 alleles increases). Finally, there is a unanimous and major effect of APOE4 on amyloid deposition with an increase in Aβ load as the number of APOE4 alleles increases and a decrease in the age of predicted amyloid-positivity in APOE4 carriers. This graded effect of APOE4 on atrophy, hypometabolism, and amyloid deposition is consistent with multimodal neuroimaging studies suggestive of a predominant effect of APOE4 on amyloid rather than tau-related injury and on brain metabolism rather than brain structure. Neuroimaging studies also suggest that APOE4 effects may be mediated by both Aβ-dependent and Aβ-independent pathological processes. This contradicts the view that Aβ pathology is a necessary upstream event to neuronal injury in AD. Perspectives and conclusion. Future studies would tell whether the mechanisms and sequences evidenced in carriers is comparable to those found in non carriers, but it is likely that APOE4 not only influences the risk for AD, but also modulates the physiopathological cascade. Altogether, APOE4 carriers offer a great opportunity to investigate brain changes in the asymptomatic stages of AD and to further our understanding of the physiopathology of the disease, although precaution is needed for interpretation in AD at large. Etat des connaissances. De très nombreuses études ont évalué les effets de l'APOE4 sur la structure cérébrale. Les résultats sont très divergents, même s'ils suggèrent dans l'ensemble un effet subtile dans le sens d'une diminution de volume dans les régions les plus sensibles à la MA telles que l'hippocampe. Les rares études en TEP-FDG indiquent une baisse du métabolisme là encore dans les régions altérées précocement dans la MA comme le cortex associatif pariétal postérieur, avec un effet dose-dépendant (i.e. fonction du nombre d'allèles APOE4). Enfin, l'effet sur les d...

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Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E ϵ4 allele

Cited by 92 publications

References 22 publications

The Effect of Apolipoprotein Polymorphism on Brain in Mild Cognitive Impairment: A Voxel-Based Morphometric Study

The Effect of Apolipoprotein Polymorphism on Brain in Mild Cognitive Impairment: A Voxel-Based Morphometric Study

APOE ε4 and cognitive function in early life: A meta-analysis.

Neuroimaging biomarkers for Alzheimer's disease in asymptomatic APOE4 carriers

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