High-throughput quantitative histological analysis of Alzheimer's disease pathology using a confocal digital microscanner

To develop a rapid method of quantifying immunohistochemical information in tissue sections, we tested a confocal laser fluorescence microscanner init ially designed for DNA microarray analysis. This instrument collects digita l images at multiple wavelengths, scans entire sections at a resolution of 5 or 10 mu m in less than 10 min, and quantifies structures labeled with fl uorescent or nonfluorescent probes. We assessed the microscanner by studyin g immunostained amyloid plaques in the Alzheimer's disease (AD) brain and i n the brain of a transgenic mouse model of AD amyloidosis, as efforts to co rrelate measures of amyloid plaques in brain sections with behavioral impai rments are impeded by limitations in current morphometric methods. Microsca nner analysis was used to determine amyloid burden in the occipital and ent orhinal cortices of the mouse (3.7%) and human AD brain (1.6%). We also qua ntified the colocalization of plaque beta-amyloid (A beta) with glial fibri llary acidic protein, a marker of gliosis (mouse 0.9%, human AD 3.7%), The microscanner may be generally applicable to a wide variety of human histopa thologies and their animal models, wherever rapid unbiased quantitative ana lysis is needed.