# Human Prion Disease: Pathogenesis, Diagnosis and Public Health

## TL;DR

This paper reviews the causes, diagnosis, and public health implications of human prion diseases, highlighting the challenges in treating these fatal neurodegenerative disorders.

## Contribution

The paper provides an updated narrative review of prion disease pathogenesis, diagnostic advancements, and therapeutic strategies, including a clinical case of iatrogenic transmission.

## Key findings

- PrP^Sc is confirmed to drive neurodegeneration and transmissibility in prion diseases.
- RT-QuIC is identified as a highly specific and sensitive diagnostic tool for prion diseases.
- Current therapeutic options have limited efficacy, but monoclonal antibodies and gene-based interventions show promise.

## Abstract

Background: Prion diseases represent a group of rare, progressive, and invariably fatal neurodegenerative disorders. Their hallmark is the infectious nature of the misfolded prion protein (PrP^Sc), which propagates by inducing conformational changes in the physiological form (PrP^C). Despite advances in basic science, these disorders still pose major clinical and therapeutic challenges. Methods: A narrative review of the scientific literature was conducted across major biomedical databases, including PubMed, Scopus, Web of Science, and Google Scholar, covering publications up to January 2025. In addition, we describe an illustrative clinical case of a young patient with probable iatrogenic Creutzfeldt–Jakob disease following corneal transplantation, used to highlight diagnostic uncertainty and infection-control implications. Findings: Evidence confirms that PrP^Sc drives neurodegenerative processes and transmissibility, with phenotypic and genetic variants influencing clinical course and prognosis. From a diagnostic perspective, neuroimaging techniques and cerebrospinal fluid biomarkers have undergone substantial refinement, with RT-QuIC emerging as a highly specific and sensitive assay. Therapeutic options remain unsatisfactory: no treatment has shown a significant impact on survival. However, innovative strategies (including monoclonal antibodies, gene-based interventions, and modulation of PrP^C) represent promising avenues of investigation. Conclusions: Prion diseases remain an unresolved challenge at the intersection of neurology and infectious diseases. Earlier diagnosis through advanced biomarkers and continued development of targeted therapies are essential to improve patient management, while the persistence of iatrogenic cases underscores the ongoing relevance of surveillance and preventive strategies in clinical practice.