Quantitative imaging for clinicopathological correlates in Alzheimer disease

A microscopic imaging system for quantifying the percentage area labeled by immunohistochemical markers (i.e., load) was developed including a three-dimensional motorized stage with microcomputer control and image analysis software. We also developed a technique to correct for batch to batch staining variability. We used this system and technique to quantify the load of Aβ and τ, two proteins implicated as a cause of Alzheimer disease. We found the mean Aβ load in the hippocampus correlates with the severity of dementia as measured by neuropsychological tests. In addition, the mean τ load in the frontal cortex correlates with the duration of dementia. Although expected, correlation of the amounts of these proteins with clinical data has eluded many researchers thus far. Our success is due, in part, to the technique that we have developed. The relevance of these findings highlights the usefulness of quantitative microscopic imaging in Alzheimer disease