The mean Aβ load in the hippocampus correlates with duration and severity of dementia in subgroups of Alzheimer disease

Abstract

Using image analysis techniques to quantify the percentage area covered by the immunopositive marker for amyloid β-peptide (Aβ), 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 Aβ loads, in the hippocampus of each subject. There were no statistically significant differences in the mean Aβ load between familial and sporadic AD subjects. Although sample sizes were too small for statistical testing, subjects with the ε4/ε4 allele of the apolipoprotein E (ApoE) gene had higher mean Aβ loads than those with the ε3/ε3 or ε3/ε4 alleles. Members of the Volga German families (recently linked to chromosome 1) all had high mean Aβ loads, and one of the chromosome 14-linked subjects had the highest mean Aβ 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 Aβ load in the hippocampus, but not with the maximum Aβ load. This difference indicates that the mean Aβ load may be a more useful feature than the maximum Aβ 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.