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Using image analysis techniques to quantify the percentage area covered by the immunopositive marker for amyloid beta-peptide (A beta), we examined subjects with combinations of either early-onset or late-onset Alzheimer disease (AD) and either familial Alzheimer disease (FAD) or sporadic Alzheimer disease (SAD). We measured the mean and maximum A beta loads, in the hippocampus of each subject. There were no statistically significant differences in the mean A beta load between familial and sporadic AD subjects. Although sample sizes were too small for statistical testing, subjects with the epsilon 4/epsilon 4 allele of the apolipoprotein E (ApoE) gene had higher mean A beta loads than those with the epsilon 3/epsilon 3 or epsilon 3/epsilon 4 alleles. Members of the Volga German families (recently linked to chromosome 1) all had high mean A beta loads, and one of the chromosome 14-linked subjects had the highest mean A beta load while the other had a relatively small load, but the sample was too small for statistical comparisons. The duration of dementia and neuropsychological test scores showed a statistically significant correlation with the mean A beta load in the hippocampus, but not with the maximum A beta load. This difference indicates that the mean A beta load may be a more useful feature than the maximum A beta load as an objective neuropathological measure for cognitive status. This finding may help to improve the established methods for quantitative assessment of the neuropathological changes in AD.

The Mean Aβ Load in the Hippocampus Correlates with Duration and Severity of Dementia in Subgroups of Alzheimer Disease