Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism - PubMed (original) (raw)

Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism

Eric M Reiman et al. Proc Natl Acad Sci U S A. 2005.

Abstract

Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) epsilon4 gene dose (i.e., the number of epsilon4 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset. We previously found that cognitively normal late-middle-aged APOE epsilon4 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia. In a PET study of 160 cognitively normal subjects 47-68 years of age, including 36 epsilon4 homozygotes, 46 heterozygotes, and 78 epsilon4 noncarriers who were individually matched for their gender, age, and educational level, we now find that epsilon4 gene dose is correlated with lower CMRgl in each of these brain regions. This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk.

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Figures

Fig. 1.

Fig. 1.

Correlations between APOE ε4 gene dose and lower CMRgl (shown in blue, P < 0.005, uncorrected for multiple comparisons) in cognitively normal late-middle-aged persons are projected onto the lateral and medial surfaces of the left and right cerebral hemispheres and shown in relationship to CMRgl reductions (purple and dark blue) found in previously described patients with Alzheimer's dementia (2) (purple and dark blue). Significant correlations were observed bilaterally in the precuneus (PCu), posterior cingulate (PC), left and right parietotemporal (PT), and left frontal (F) regions preferentially affected by AD (dark blue), and in adjacent PC, PCu, PT, and F regions (light blue).

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