Article

Apolipoprotein E Genotype is Associated with Temporal and Hippocampal Atrophy Rates in Healthy Elderly Adults: A Tensor-Based Morphometry Study

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7226, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 01/2011; 23(3):433-42. DOI: 10.3233/JAD-2010-101398
Source: PubMed

ABSTRACT Apolipoprotein E (ApoE) ε4 genotype is a strong risk factor for developing Alzheimer's disease (AD). Conversely, the presence of the ε2 allele has been shown to mitigate cognitive decline. Tensor-based morphometry (TBM), a novel computational approach for visualizing longitudinal progression of brain atrophy, was used to determine whether cognitively intact elderly participants with the ε4 allele demonstrate greater volume reduction than those with the ε2 allele. Healthy "younger elderly" volunteers, aged 55-75, were recruited from the community and hospital staff. They were evaluated with a baseline and follow-up MRI scan (mean scan interval = 4.72 years, s.d. = 0.55) and completed ApoE genotyping. Twenty-seven participants were included in the study of which 16 had the ε4 allele (all heterozygous ε3ε4 genotype) and 11 had the ε2ε3 genotype. The two groups did not differ significantly on any demographic characteristics and all subjects were cognitively "normal" at both baseline and follow-up time points. TBM was used to create 3D maps of local brain tissue atrophy rates for individual participants; these spatially detailed 3D maps were compared between the two ApoE groups. Regional analyses were performed and the ε4 group demonstrated significantly greater annual atrophy rates in the temporal lobes (p = 0.048) and hippocampus (p = 0.016); greater volume loss was observed in the right hippocampus than the left. TBM appears to be useful in tracking longitudinal progression of brain atrophy in cognitively asymptomatic adults. Possession of the ε4 allele is associated with greater temporal and hippocampal volume reduction well before the onset of cognitive deficits.

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    • "Regarding longitudinal MRI studies, results in elderly are more consistent. Most studies highlighted a faster rate of grey matter atrophy in APOE4 carriers compared with non-carriers, especially in medial temporal structures (Cohen et al. 2001; Chen et al. 2007; Morra et al. 2009; Donix et al. 2010a; Hua et al. 2010; Risacher et al. 2010; Chiang et al. 2011; Lu et al. 2011; Roussotte et al. 2014), although negative findings have also been reported (Jack et al. 1998; Du et al. 2006; Schuff et al. 2009; Taylor et al. 2014). In contrast, normal elderly APOE2 carriers showed a slower rate of hippocampal grey matter atrophy compared with APOE3 homozygotes (Chiang et al. 2011). "
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    • "The other three studies show significant DMN connectivity differences between APOE4 carriers and APOE3 homozygotes, although there is substantial variability in their results. Sheline et al. (2010) found increases and decreases in DMN connectivity in e4 carriers, Machulda et al. (2011) only found decreases, Westlye et al. (2011) only found increases, and Trachtenberg et al. (2012) found no differences in the DMN but reported differences in two hippocampal networks. None of these fMRI studies of APOE, task-based or resting state, examined whether the observed default mode functional connectivity differences varied by gender. "
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    • "Despite the high heritability of many brain measures (h 2 up to 0.89; Kremen et al. 2009; or even up to 0.96: van Soelen et al. 2012), the specific genetic variants that contribute to this variability remain largely unknown. A possible exception is the Alzheimer's disease (AD) risk gene, APOE: carriers of one or more risk-conferring alleles (APOE4 ) demonstrate accelerated gray matter loss with age (Lu et al. 2011). They also have a roughly three-fold increased risk for late-onset AD, for each risk allele they carry (Corder et al. 1993). "
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