This document summarizes prion diseases, which are a group of progressive neurodegenerative disorders known as transmissible spongiform encephalopathies. The diseases affect both animals like sheep and deer, as well as humans. They are caused by misfolded prion proteins that form plaques in the central nervous system, disrupting normal tissue structure and causing holes or vacuoles in neurons. Prion diseases have a long incubation period, cause neurologic symptoms, and are ultimately fatal. Key features include spongiosis, gliosis, and neuronal loss. The diseases can be sporadic, genetic, or acquired through infection or medical procedures.

2. • Pr
ion

3. Prion Diseases
Animals
• Scrapie (sheep)
• Bovine spongiform
encephalopathy (BSE)
• Chronic wasting disease
(CWD) (deer & elk)
Humans
• Kuru
• Creutzfeldt-Jakob disease
(CJD)
• Fatal familial insomnia
• Gerstmann-Sträussler-
Scheinker disease
Family of diseases known as the transmissible spongiform
encephalopathies (TSEs)
• Prolonged incubation period of several years – depends on the
disease
• Progressive debilitating neurologic syndrome - invariably fatal
• Pathological changes confined to the CNS with classic features -
spongiosis, gliosis, and neuronal loss
• Transmissible agent does not elicit any specific immunologic
response

5. • Cause neurodegenerative disease by aggregating
amyloid plaques the central nervous system
• Disrupt the normal tissue structure.
• "holes" in the tissue - spongy architecture due to the
vacuole formation in the neurons.
• Astrogliosis
• Absence of an inflammatory reaction.
• Classical features - spongiosis, gliosis, and
neuronal loss

8. Physiological processes of the
native prion protein (PrPc)
PrPC + Cu
(Copper)

Antioxidant
activity

Resistance to
oxidative stress

Prevent neuronal
dysfunction

10. Polymerisation
PrPC PrP*
PrPSc
PrPSc
PrP*
Dimerisation
PrPSc PrPSc
PrPC PrP* PrPSc
PrP*
PrPSc

11. • PrPC PrPSC
Solubility
• Soluble Non soluble
Structure
• Alpha-helical Beta-sheeted
Multimerisation state
• Monomeric Multimeric
Infectivity
• Non infectious Infectious
Susceptibility to Proteinase K
• Susceptible Resistant

12. Etiology
• Sporadic (85%)
• Most commonest
• Spontaneous PrPC to PrPSc conversion or somatic
mutation
• sporadic Creutzfeldt-Jakob disease (sCJD)
• Genetic/familial (15%)
• caused by defects in the PrP gene - short arm of
chromosome 20
• autosomal dominant
• familial CJD (fCJD), fatal familial insomnia

13. • Acquired/Infectious (<1%)
• Kuru – Highlands of New Guinea, ritualistic
cannibalism
• Iatrogenic CJD
• organ and tissue transplants,
• use of contaminated surgical instruments
• dura mater grafts
• human pituitary-derived gonadotrophins, and human-
derived growth hormone.
• Blood transfusions – theoretical risk based on
experimental studies in animals– no reported cases
• Variant CJD
• ingestion of beef products contaminated with BSE
• Small number of transfusion transmitted cases
reported in uk