The influence of the ApoE genotype on regional amyloid beta progression and interregional correlations in nondemented elderly

Abstract

AbstractBackgroundPrevious examinations have explored the spatiotemporal pattern of amyloid beta (Ab) deposition, one of the first pathogenic events in Alzheimer’s disease (AD). However, the literature presents with a limited characterization of early spatial Ab progression differences and interregional correlations related to the major genetic AD risk factor, the Apolipoprotein E (ApoE) genotype.MethodThe impact of ApoE genotype on dynamic spatiotemporal Ab patterns was investigated using longitudinal amyloid positron emission tomography (PET) imaging. A first analysis used data of 100 nondemented participants who were characterized as having an Ab increase over time. Standardized uptake value ratios (SUVRs) of 31 cortical and subcortical regions were extracted. Regional average SUVRs were clustered per genotype based on longitudinal trajectory shapes. A second analysis focused on the ApoE genotype impact on interregional correlations of annual change rates in 81 cognitively normal individuals. We explored the difference in the distribution of correlations and performed permutation statistics. All analyses were replicated and validated applying partial volume correction.ResultE4 carriers and noncarriers displayed different regional Ab trajectories. In general, noncarriers displayed a more homogeneous Ab increase over time in comparison to more diverse trajectories in carriers. Six regional clusters ranging from lowest Ab‐baseline values and none‐to‐small increases (cluster 1) to highest Ab‐baseline values and considerable increases (cluster 6) were identified for both carriers and noncarriers. Independent of genotype, cluster 1 contained the amygdala, the medial part of the anterior temporal lobe, the caudate nucleus, the parahippocampal gyrus, the anterior part of the superior temporal gyrus, and the hippocampus. Other clusters differed between genotypes with several regions being assigned to higher Ab‐baseline and higher increase clusters in carriers. The correlational analysis found a distinct pattern in noncarriers with most regions presenting significant positive intercorrelations except for the hippocampus, which demonstrated almost exclusively null‐to‐negative correlations. This pattern was not found in e4 carriers.ConclusionThe results suggested an ApoE genotype impact on the heterogeneity of the spatiotemporal Ab pattern and a dissociative hippocampal role.