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

BACKGROUND:Carriers of the ApoE 4 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 4 carriers and non-carriers, few have characterized these differences in terms of brain region and neuropathological score frequency.METHODS:566 pathologically-confirmed AD cases who were followed prospectively with antemortem dementia diagnoses (312 ApoE 4 carriers and 254 ApoE 4 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 (4 carrier vs. 4 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).RESULTS:4 carriers had a significantly lower age at death (p <0.001) and significantly higher Braak scores (p <0.001) than 4 non-carriers. Genotype comparison revealed that plaque and tangle pathologies increased in the following pattern, 2/3<3/3<2/4<3/4