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Introduction to Prion Diseases

  • Focus on diseases caused by misfolded proteins
  • Examples include Creutzfeldt-Jakob disease (CJD), Mad Cow Disease (BSE), and Kuru

Case Study: Patient Presentation

  • Patient Profile: 56-year-old female with sudden muscular and vision issues after a trip to the UK
    • Symptoms: Jerking movements in limbs, blurred vision
  • Differential Diagnosis:
    • Nervous system/brain disorder (potential stroke or tumor)
    • Musculoskeletal disorder
    • Endocrine/metabolism disorder
    • Cancer
    • Vascular disorder
    • Nutritional/environmental factors
    • Infectious/immune disorder

Sudden Onset Investigation

  • Factors considered for sudden onset of symptoms:
    • Change in nutrition or environment
    • Infections
    • Late onset diseases (e.g. metabolic conditions)
    • Dementia-related conditions (e.g. menopause)

Progression of Symptoms

  • After initial consultation, further symptoms developed:
    • Malaise, sleep disturbances, loss of taste and smell, hallucinations
    • Cognitive decline, inability to perform simple tasks
  • Diagnostic Tests Conducted:
    • Optical exam and MRI: No lesions detected
    • CSF and serological tests: No infections found

Diagnosis and Misdiagnosis

  • Initial Diagnosis: Alzheimer’s Disease due to age and cognitive decline settings
  • Unremarkable neurological examination and negative genetic risk factors for Alzheimer's
  • Final diagnosis: Creutzfeldt-Jakob Disease (CJD) confirmed via brain biopsy showing antibodies against mutant PrP protein

Understanding Creutzfeldt-Jakob Disease

  • Characteristics:
    • Rare neurodegenerative disorder, often confused with Alzheimer’s
    • Rapid onset with a long latency period;
    • Survival duration post-diagnosis averages around 13-14 months
  • Incidence: 1-2 cases per million annually

Prions

  • Definition: Infectious proteins without genetic material, defined as proteinaceous infectious particles
    • First identified by Stanley Prusiner in 1982, Nobel Prize in 1997
  • Characteristics of prions:
    • Smaller than viruses
    • Resistant to UV and various solvents

Types and Examples of Prion Diseases

  • Transmissible spongiform encephalopathies:
    • Bovine spongiform encephalopathy (BSE) - Mad Cow Disease
    • Kuru (affects certain PNG tribes)
    • Fatal Familial Insomnia (FFI) - inherited
  • Lack of Treatment: Currently, no known cure for prion diseases

Mechanism Behind Prion Diseases

  • Alterations in Prion Protein (PrP) can lead to disease:
    • Changes in structure lead to different functions or accumulation
    • Misfolding can disrupt normal cellular mechanisms

Protein Aggregation and Disease

  • Mechanism: Protein aggregates (like amyloids) resist decomposition and damage cells
    • Accumulate as fibrils and disrupt cellular functions
  • Effects of Aggregation:
    • Extracellular aggregates damage surrounding tissues
    • Intracellular aggregates disturb normal cellular processes

Resistance to Proteolysis

  • Structural Resilience: Protein aggregates resist enzymatic breakdown due to their fibril arrangement

Learning Goals

  • Grasp the concept of protein aggregation and its roles in disease causation
  • Understand prion biology and their infectious behaviors