Prion Diseases: A Unique Transmissible Agent or a Model for Neurodegenerative Diseases?

Abstract

The accumulation and propagation in the brain of misfolded proteins is a pathological hallmark shared by many neurodegenerative diseases such as Alzheimer’s disease (Aβ and tau), Parkinson’s disease (α-synuclein), and prion disease (prion protein). Currently, there is no epidemiological evidence to suggest that neurodegenerative disorders are infectious, apart from prion diseases. However, there is an increasing body of evidence from experimental models to suggest that other pathogenic proteins such as Aβ and tau can propagate in vivo and in vitro in a prion-like mechanism, inducing the formation of misfolded protein aggregates such as amyloid plaques and neurofibrillary tangles. Such similarities have raised concerns that misfolded proteins, other than the prion protein, could potentially transmit from person-to-person as rare events after lengthy incubation periods. Such concerns have been heightened following a number of recent reports of the possible inadvertent transmission of Aβ pathology via medical and surgical procedures. This review will provide a historical perspective on the unique transmissible nature of prion diseases, examining their impact on public health and the ongoing concerns raised by this rare group of disorders. Additionally, this review will provide an insight into current evidence supporting the potential transmissibility of other pathogenic proteins associated with more common neurodegenerative disorders and the potential implications for public health.

Understanding Intra-Species and Inter-Species Prion Conversion and Zoonotic Potential Using Protein Misfolding Cyclic Amplification

“…Apart from secondary transmission of vCJD via blood or blood products ( Peden et al, 2004 ; Urwin et al, 2016 ), iCJD also includes cases acquired by the use of contaminated medical instruments ( Bernoulli et al, 1977 ; Will and Matthews, 1982 ), transplantation of contaminated corneal grafts ( Duffy et al, 1974 ), cadaveric dura mater (DM-iCJD) ( Brown et al, 2012 ), or treatment with contaminated cadaveric growth hormone (GH-iCJD) ( Gibbs et al, 1985 ; Koch et al, 1985 ; Powell-Jackson et al, 1985 ; Ritchie et al, 2017 ). DM-iCJD and GH-iCJD comprise the majority of iCJD cases worldwide ( Brown et al, 2012 ; Ritchie and Barria, 2021 ).…”

Is Multiple System Atrophy a Prion-like Disorder?

“…The ability of prions to self-propagate allows them to spread within host tissues and underlies the transmissible nature of the prion disorders with the capacity to spread between individuals or species [ 81 ]. Various proteins have been shown to spread between cells and tissues of the host (for reviews see [ 82 , 83 , 84 ]), but there is no clear evidence of transmission between individuals, at least by artificial or natural routes [ 85 , 86 , 87 ]. As the risk of clinical transmission of proteinopathies between humans is critically evaluated, the scenarios for PrP-based prion diseases and their many experimental models must be considered.…”

Prion Protein: The Molecule of Many Forms and Faces

“…It exists in two forms; the normal or cellular isoform, PrP C , and the disease-associated infectious isoform or scrapie PrP, PrP Sc . The pathological role of PrP Sc has been extensively studied in prion disease and has been reviewed in several papers [1][2][3]. PrP C is expressed in a variety of different organs and tissues with high expression levels in the central and peripheral nervous systems.…”