Abnormal prion protein deposits with high seeding activities in the skeletal muscle, femoral nerve, and scalp of an autopsied case of sporadic Creutzfeldt–Jakob disease

Abstract

We report the general autopsy findings of abnormal prion protein (PrP) deposits with their seeding activities, as assessed by the real-time quaking-induced conversion (RT-QuIC) method, in a 72-year-old female patient with sporadic Creutzfeldt-Jakob disease (sCJD). At 68 years of age, she presented with gait disturbance and visual disorders. Electroencephalography showed periodic synchronous discharge. Myoclonus was also observed. A genetic test revealed that PRNP codon 129 was methionine/methionine (MM). She died of pneumonia three years and four months after disease onset, and a general autopsy was performed. The brain weighed 650 g and appeared markedly atrophic. Immunohistochemistry for PrP revealed synaptic PrP deposits and coarse PrP deposits in the cerebral cortices, basal ganglia, cerebellum, and brainstem. Western blot analysis identified type 1 proteinase-Kresistant PrP in frontal cortex samples. PrP deposits were also observed in systemic organs, including the femoral nerve, psoas major muscle, abdominal skin, adrenal medulla, zona reticularis of the adrenal gland, islet cells of the pancreas, and thyroid gland. The RT-QuIC method revealed positive seeding activities in all examined organs, including the frontal cortex, femoral nerve, psoas major muscle, scalp, abdominal skin, adrenal gland, pancreas, and thyroid gland. The following 50% seeding dose (SD 50 ) values were 9.5 (frontal cortex); 8 AE 0.53 (femoral nerve); 7 AE 0.53 (psoas major muscle); and 7.88 AE 0.17 (scalp). The SD 50 values for the adrenal gland, dermis, pancreas, and thyroid gland were 6.12 AE 0.53, 5.25, 4.75, and 4.5, respectively. PrP deposits in general organs may be associated with long-term disease duration. This case indicated the necessity for general autopsies in sCJD cases to establish strict infection control procedures for surgical treatment and to examine certain organs.

In Vitro and In Vivo Evidence towards Fibronectin’s Protective Effects against Prion Infection

“…In natural scrapie, we reported that PrP Sc associated with intramuscular nerve fibers and neuromuscular spindles [10]. The same affected nerve structures have been described in experimental scrapie [9], human prion diseases [14,15], experimental infections with BSE [16,17] and hamsters inoculated with transmissible mink encephalopathy [18]. Thus, in vivo experiments have not shown clear prion deposition in myofibers of striated muscle.…”

“…The accumulation of PrP Sc in striated muscle tissue of prion-infected animals is associated with nerve structures rather than myofibers [10,[12][13][14][15], suggesting that there is an inefficient environment for prion replication and/or accumulation in this cell type. Conversely, myotubes, the myofiber counterpart in dC2C12 cell culture, become susceptible to prion infection when they mature from their prion-resistant myoblast precursors.…”

Characteristic distribution and molecular properties of normal cellular prion protein in human endocrine and exocrine tissues

“…For example, PrP Sc was detected in the adrenal medulla in cattle affected with bovine spongiform encephalopathy and scrapie-infected sheep 20 , 21 . In humans, we previously reported PrP Sc aggregation in the adrenal medulla of sCJD patients and enhanced seeding activity on real-time quaking-induced conversion 22 . Our results suggested that PrP c in the adrenal medulla may be the source of PrP Sc .…”

“…In some prion diseases, abnormal PrP deposits have been identified in systemic organs other than the central nervous system 2 – 4 . Prion disease is characterized by the conversion of a normal cellular prion protein isoform (PrP c ) into an abnormal pathogenic PrP (scrapie prion protein: PrP Sc ).…”

A Comprehensive Systematic Review of YOLO for Medical Object Detection (2018 to 2023)

“…and other clinically relevant medical objects [33], [34]. It can detect and localize abnormalities in medical images, which can aid in the early detection and diagnosis of various diseases, including breast cancer, lung cancer, narrowing of blood vessels [35], brain atrophy [36], and abnormal protein deposits [37], cardiovascular diseases [38], and neurological disorders [39]. The adoption of YOLO in medical applications has the potential to improve the accuracy and efficiency of medical diagnosis, which can have a significant impact on patient outcomes.…”