Comparing Gallyas and AT8 staining for quantification of tau pathology in subregions of the human hippocampus

Gallyas silver staining and AT8 immunostaining are frequently used to stage tau pathology in post-mortem Alzheimer disease (AD) brains. Because of differential labeling of tau aggregation types, however, these methods result in strikingly different patterns of pathology when used in adjacent sections of the same brain. How Gallyas versus AT8 staining impacts the quantification of tau pathology distribution across brain areas and affect analysis of tau and cognitive impairment is unknown. We performed a side-by-side comparison of AT8 versus Gallyas-stained hippocampal sections from 34 patients from the University of Southern California (USC) Alzheimer's Disease Research Center (ADRC). Using images of Gallyas and AT8 stained sections, we computed overall tau density in hippocampal subregions as well as manual tangle counts and compared each of them to cognitive variables like Clinical Dementia Rating and Mini Mental State Exam in the patients. We found that AT8 had a much higher density of staining overall, and the two stains had differing distributions, with increased AT8 in Brodmann area 35 and CA1. Both stains related to cognition differentially, and Gallyas density was significantly related to post-mortem interval. These findings contribute to our understanding of how tau pathology stain choice might influence the characterization of AD.