The influence of Apolipoprotein E genotype on regional pathology in Alzheimer’s disease

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Abstract
Carriers of the ApoE ϵ4 allele are at a greater risk for developing Alzheimer’s disease (AD) and those who do develop AD tend to have a much greater neuropathological disease burden. Although several studies have shown significant differences in AD pathology among ϵ4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency. 566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE ϵ4 carriers and 254 ApoE ϵ4 non-carriers) were compared on the frequencies of neuropathological frequency scores (none, sparse, moderate, frequent) among several different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal) using the CERAD scoring system. Pathology score frequencies were analyzed by carrier status (ϵ4 carrier vs. ϵ4 non-carrier) and by genotype (2/3, 3/3, 2/4, 3/4, 4/4). Both analyses investigated pathology score frequencies among different brain regions (frontal, temporal, parietal, hippocampal, and entorhinal). ϵ4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than ϵ4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4<4/4, for several brain regions. When stratified by age and ApoE ϵ4 carrier status, ϵ4 carriers tended to have significantly more frequent scores across most cortical areas. However, non-carriers age 90 and older tended to have greater plaque pathology than carriers. For tangle pathology, ϵ4 carriers tended to have significantly more “frequent” scores than non-carriers, except for the hippocampal and entorhinal areas in individuals age 90 and older. ApoE ϵ4 carriers had a significantly higher percentage of “frequent” scores for plaques and tangles when compared to ApoE ϵ4 non-carriers for several brain regions. However, ϵ4 non-carriers age 90 and older tended to have less plaque and tangle pathology in certain brain regions. These results demonstrate that AD pathology may manifest itself differently based on ApoE genotype and suggest that ApoE carriers and non-carriers may have different patterns of AD neuropathology location and density.

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