Scientific Publications by FDA Staff

J Histochem Cytochem 2006 Jan;54(1):97-107

Computerized Morphometric Analysis of Pathological Prion Protein Deposition in Scrapie-Infected Hamster Brain.

Maximova OA, Taffs RE, Pomeroy KL, Piccardo P, Asher DM

Maximova OA, US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Rev,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-313, Rockville, MD 20852 USA US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Rev,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA

Transmissible spongiform encephalopathies (TSEs or prion diseases) are characterized by a constellation of typical though variable pathological changes in the brain. Deposition of disease-associated abnormal prion protein (PrP(Sc)) is the pathological feature of TSEs most consistent and accessible for quantification. However, the evaluation of PrP(Sc) deposits detected by immunohistochemical techniques has been traditionally based on arbitrarily assigned semi-quantitative scores. This approach is limited by its subjectivity and bias, yielding considerable variability. In this study, we used MetaMorph 6.1 image analysis software for quantitative analysis of immunostained PrP(Sc) deposits in the CNS of hamsters infected with the 263K strain of scrapie agent. Computerized morphometric analysis (CMA) allowed unambiguous detection of even minimal amounts of immunostained PrP(Sc). CMA values for intensity of staining and area stained correlated well with semi-quantitative scores, providing reproducible quantitative data and objective criteria for analyzing PrP(Sc) deposition. CMA provides a simple and reliable method for improved and consistent diagnosis of TSEs that may also be used to quantify other immunostained biomarkers.