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

To develop a rapid method of quantifying immunohistochemical information in tissue sections, we tested a confocal laser fluorescence microscanner initially designed for DNA microarray analysis. This instrument collects digital images at multiple wavelengths, scans entire sections at a resolution of 5 or 10 microm in less than 10 min, and quantifies structures labeled with fluorescent or nonfluorescent probes. We assessed the microscanner by studying immunostained amyloid plaques in the Alzheimer's disease (AD) brain and in the brain of a transgenic mouse model of AD amyloidosis, as efforts to correlate measures of amyloid plaques in brain sections with behavioral impairments are impeded by limitations in current morphometric methods. Microscanner analysis was used to determine amyloid burden in the occipital and entorhinal cortices of the mouse (3.7%) and human AD brain (1.6%). We also quantified the colocalization of plaque beta-amyloid (Abeta) with glial fibrillary 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 histopathologies and their animal models, wherever rapid unbiased quantitative analysis is needed.