Lack of Prion Infectivity in Fixed Heart Tissue from Patients with Creutzfeldt-Jakob Disease or Amyloid Heart Disease

Abstract

In most forms of prion disease, infectivity is present primarily in the central nervous system or immune system organs such as spleen and lymph node. However, a transgenic mouse model of prion disease has demonstrated that prion infectivity can also be present as amyloid deposits in heart tissue. Deposition of infectious prions as amyloid in human heart tissue would be a significant public health concern. Although abnormal disease-associated prion protein (PrP Sc ) has not been detected in heart tissue from several amyloid heart disease patients, it has been observed in the heart tissue of a patient with sporadic Creutzfeldt-Jakob Disease (sCJD), the most common form of human prion disease. In order to determine whether prion infectivity can be found in heart tissue, we have inoculated formaldehyde fixed brain and heart tissue from two sCJD patients, as well as prion protein positive fixed heart tissue from two amyloid heart disease patients, into transgenic mice overexpressing the human prion protein. Although the sCJD brain samples led to clinical or subclinical prion infection and deposition of PrP Sc in the brain, none of the inoculated heart samples resulted in disease or the accumulation of PrP Sc . Thus, our results suggest that prion infectivity is not likely present in cardiac tissue from sCJD or amyloid heart disease patients.

Familial human prion diseases associated with prion protein mutations Y226X and G131V are transmissible to transgenic mice expressing human prion protein

“…The sensitivity of tg66 mice to transmission of human sCJD and vCJD was reported previously [ 37 , 38 ], and this sensitivity was emphasized in the present study by the transmission of infectivity from Y226X brain obtained from formalin-fixed tissue sections which were removed from microscope slides. Previous experiments have shown that prion infectivity is only partially sensitive to treatment with formalin [ 40 ], and can be obtained from formalin-fixed brain [ 2 , 15 , 32 , 35 ]. In the case of Y226X, formalin-fixed brain was the only tissue available, even in the initial description of this patient [ 23 ].…”

Detection and Quantification of CWD Prions in Fixed Paraffin Embedded Tissues by Real-Time Quaking-Induced Conversion

“…Previous studies have established protocols for the isolation of disease associated prion proteins from formalin-fixed paraffin-embedded tissue sections 8 9 10 . Transgenic mice expressing hamster PrP C intracerebrally inoculated with prions isolated from formaldehyde fixed paraffin-embedded 263K scrapie strain terminal brains developed clinical disease 8 .…”

“…Previous studies have established protocols for the isolation of disease associated prion proteins from formalin-fixed paraffin-embedded tissue sections 8 9 10 . Transgenic mice expressing hamster PrP C intracerebrally inoculated with prions isolated from formaldehyde fixed paraffin-embedded 263K scrapie strain terminal brains developed clinical disease 8 . Prion protein can be demonstrated in some archived formalin-fixed paraffin-embedded tissues and detected by western blotting, albeit with lower levels of sensitivity, typically limiting this method to terminal samples 9 10 .…”

Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes

“…The presence of amyloid plaques was confirmed by staining deparaffinized sections with the amyloid dye Thioflavin S (ThioS) as previously described [35]. Hamotoxylin and eosin (H&E) staining was performed by hand on deparaffinized slides using Shandon Instant Hemotoxylin and Eosin (Thermo Scientific) according to the manufacturer's instructions.…”