NeuroimagingHow does the apolipoprotein E genotype modulate the brain in aging and in Alzheimer’s disease? A review of neuroimaging studies
Introduction
Whereas the apolipoprotein E (ApoE) allele ϵ4 is the most significant risk factor for Alzheimer’s disease (AD) in the general population, research on the role of ApoE in relation to the pathogenesis of AD has provoked several controversies, and the exact role of the ApoE remains undetermined. For instance, it was initially reported that brains of AD patients carrying the ϵ4 allele had increased number of plaques [21], [33], [39], [41], [46], neurofibrillary tangles [33], [34], [39], and more severe cholinergic deficit [38], [50], [51] than found in those without the ϵ4 allele. These, however, were followed by subsequent studies that could not replicate or even totally contradicted these findings [4], [14], [18]. Since the primary purpose of this paper is to review neuroimaging findings in AD in relation with the ApoE genotype, we leave this debate open, and instead focus on the findings, and the controversies, that neuroimaging studies to date have suggested. We will propose that ApoE may be related with asymmetrical and regionally different patterns of AD, histopathological background of which remains unknown. By presenting these intriguing controversies, we hope that this review will be of interest even to those who are not directly involved with the field of neuroimaging.
Section snippets
ApoE and magnetic resonance imaging
In 1995, we used volumetric magnetic resonance imaging (MRI) and found that normal hippocampal right > left asymmetry was diminished in non-demented elderly subjects [52], and that hippocampal and amygdaloid damage was greater in AD patients carrying the ϵ4 allele despite equal global cognitive severity of the disease [30]. This atrophy observed in AD patients was correlated with tests assessing delayed memory and the performance of homozygotic ϵ4 carriers in these tests was inferior to
Cerebral perfusion and metabolism
There is also an increasing number of studies that have examined how the ApoE genotype can influence regional cerebral blood flow (rCBF) or glucose metabolism (rCMRGl).
In 1995, Small et al. [49] measured rCMRGl from cognitively normal subjects who fulfilled the criteria for age-associated memory impairment and had a well-documented family history of AD. They found decreased parietal metabolism and left-right asymmetry in subjects carrying the ϵ4 allele. Other regions of the brain were not
Discussion
In this review, we propose that ApoE is responsible for the region-specific changes in the AD brain, and that this may also be the case in cognitively normal subjects. Currently, it seems that ApoE ϵ4 allele is linked to increased, and perhaps asymmetric, MTL damage. Not all the studies that have addressed the question of MTL damage in relation to the ϵ4 allele have detected significantly smaller or asymmetrical patterns of the hippocampal volumes. However, in each of the reviewed studies,
Acknowledgements
This study was supported by the Research Council for Health of the Academy of Finland.
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