Article

Functional magnetic resonance imaging and magnetoencephalography differences associated with APOEε4 in young healthy adults

Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA.
Neuroreport (Impact Factor: 1.64). 11/2006; 17(15):1585-90. DOI: 10.1097/01.wnr.0000234745.27571.d1
Source: PubMed

ABSTRACT Functional neural alterations are present in middle-aged to late-aged healthy individuals carrying the epsilon4 allele of the apolipoprotein E (APOEepsilon4) gene, a known risk factor for Alzheimer's disease. Neural activity was measured in young adults with and without the epsilon4 allele (APOEepsilon4+ and APOEepsilon4-) by functional magnetic resonance imaging and magnetoencephalography while performing a visual working memory task on two separate days. Greater activity was observed in frontal areas and cingulate gyri in APOEepsilon4+ participants by both functional magnetic resonance imaging and magnetoencephalography with regional blood oxygenation level-dependent responses correlating with increased theta band power. The findings suggest that the presence of the APOEepsilon4 allele has physiological consequences before aging that may contribute to risk for Alzheimer's disease.

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    • "Furthermore, decreases in cerebral glucose metabolism are a known biomarker for AD [139], and cognitively-normal, middle-aged APOE ε4 carriers have AD-like changes in cerebral glucose metabolism [140] [141], with a possible gene-dose effect [142]. A handful of studies using functional magnetic resonance imaging of the default mode network (DMN) have also shown differential oxygen uptake in the brain at rest in young APOE ε4 carriers, indicating differences in brain metabolic function early in life [143] [144] [145]. Some have argued that default mode network changes may more closely represent actual brain oxygen consumption [146] [147] and thus mitochondrial function. "
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    ABSTRACT: Although Alzheimer's Disease (AD) is the most common neurodegenerative disease, the etiology of AD is not well understood. In some cases, genetic factors explain AD risk, but a high percentage of late-onset AD is unexplained. The fact that AD is associated with a number of physical and systemic manifestations suggests that AD is a multifactorial disease that affects both the CNS and periphery. Interestingly, a common feature of many systemic processes linked to AD is involvement in energy metabolism. The goals of this review are to 1) explore the evidence that peripheral processes contribute to AD risk, 2) explore ways that AD modulates whole-body changes, and 3) discuss the role of genetics, mitochondria, and vascular mechanisms as underlying factors that could mediate both central and peripheral manifestations of AD. Despite efforts to strictly define AD as a homogeneous CNS disease, there may be no single etiologic pathway leading to the syndrome of AD dementia. Rather, the neurodegenerative process may involve some degree of baseline genetic risk that is modified by external risk factors. Continued research into the diverse but related processes linked to AD risk is necessary for successful development of disease -modifying therapies.
    Biochimica et Biophysica Acta 04/2014; 1842(9). DOI:10.1016/j.bbadis.2014.04.012 · 4.66 Impact Factor
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    • "Furthermore, decreases in cerebral glucose metabolism are a known biomarker for AD [139], and cognitively-normal, middle-aged APOE ε4 carriers have AD-like changes in cerebral glucose metabolism [140] [141], with a possible gene-dose effect [142]. A handful of studies using functional magnetic resonance imaging of the default mode network (DMN) have also shown differential oxygen uptake in the brain at rest in young APOE ε4 carriers, indicating differences in brain metabolic function early in life [143] [144] [145]. Some have argued that default mode network changes may more closely represent actual brain oxygen consumption [146] [147] and thus mitochondrial function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Although Alzheimer’s Disease (AD) is the most common neurodegenerative disease, the etiology of AD is not well understood. In some cases, genetic factors explain AD risk, but a high percentage of late-onset AD is unexplained. The fact that AD is associated with a number of physical and systemic manifestations suggests that AD is a multifactorial disease that affects both the CNS and periphery. Interestingly, a common feature of many systemic processes linked to AD is involvement in energy metabolism. The goals of this review are to 1) explore the evidence that peripheral processes contribute to AD risk, 2) explore ways that AD modulates whole-body changes, and 3) discuss the role of genetics, mitochondria, and vascular mechanisms as underlying factors that could mediate both central and peripheral manifestations of AD. Despite efforts to strictly define AD as a homogeneous CNS disease, there may be no single etiologic pathway leading to the syndrome of AD dementia. Rather, the neurodegenerative process may involve some degree of baseline genetic risk that is modified by external risk factors. Continued research into the diverse but related processes linked to AD risk is necessary for successful development of disease –modifying therapies.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 01/2014; · 5.09 Impact Factor
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    • "Specifically within younger cohorts some studies suggest that neuronal deficits related to the E4 carrier genotype may lead to greater recruitment of functional activation in order to reach the same level of cognitive performance as E4 non-carriers [27]–[29]. Other studies have failed to find cognitive differences by ApoE genotype in younger subjects [30], while still more studies have found evidence for beneficial effects of the E4 carrier genotype in young people [26], [31]. "
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    ABSTRACT: The E4 allele of the ApoE gene has consistently been shown to be related to an increased risk of Alzheimer's disease (AD). The E4 allele is also associated with functional and structural grey matter (GM) changes in healthy young, middle-aged and older subjects. Here, we assess volumes of deep grey matter structures of 22 healthy younger ApoE4 carriers and 22 non-carriers (20-38 years). Volumes of the nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen, thalamus and brain stem were calculated by FMRIB's Integrated Registration and Segmentation Tool (FIRST) algorithm. A significant drop in volume was found in the right hippocampus of ApoE4 carriers (ApoE4+) relative to non-carriers (ApoE4-), while there was a borderline significant decrease in the volume of the left hippocampus of ApoE4 carriers. The volumes of no other structures were found to be significantly affected by genotype. Atrophy has been found to be a sensitive marker of neurodegenerative changes, and our results show that within a healthy young population, the presence of the ApoE4+ carrier gene leads to volume reduction in a structure that is vitally important for memory formation. Our results suggest that the hippocampus may be particularly vulnerable to further degeneration in ApoE4 carriers as they enter middle and old age. Although volume reductions were noted bilaterally in the hippocampus, atrophy was more pronounced in the right hippocampus. This finding relates to previous work which has noted a compensatory increase in right hemisphere activity in ApoE4 carriers in response to preclinical declines in memory function. Possession of the ApoE4 allele may lead to greater predilection for right hemisphere atrophy even in healthy young subjects in their twenties.
    PLoS ONE 11/2012; 7(11):e48895. DOI:10.1371/journal.pone.0048895 · 3.23 Impact Factor
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