Creutzfeldt-Jakob disease pathophysiology

Creutzfeldt-Jakob disease Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Creutzfeldt-Jakob disease from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Creutzfeldt-Jakob disease pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Creutzfeldt-Jakob disease pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Creutzfeldt-Jakob disease pathophysiology
CDC on Creutzfeldt-Jakob disease pathophysiology
Creutzfeldt-Jakob disease pathophysiology in the news
Blogs on Creutzfeldt-Jakob disease pathophysiology
Directions to Hospitals Treating Psoriasis
Risk calculators and risk factors for Creutzfeldt-Jakob disease pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2], Mohamadmostafa Jahansouz M.D.[3]

Overview

The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission. Reports on transmission by human growth hormone products, grafting, surgical electrode implantation, and consumption of infected products have been described. Once transmitted, the CJD prion promotes refolding of the native proteins into the diseased state. The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells, resulting in cell death. On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue. On microscopic histopathological analysis, spongiform changes, neuronal loss, astrocyte proliferation, and deposition of prion proteins in the brain are characteristic findings.

Pathophysiology

Transmission

• The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission.
• The defective protein associated with Creutzfeldt-Jakob disease can be inherited (familial form) or transmitted (iatrogenic form) through the following:
  • Human growth hormone (hGH) products
  • Corneal grafting
  • Dural grafts or electrode implants
  • Use of HGH drawn from the pituitary glands of cadavers
  • Consumption of infected animals
  • Cannibalism
• The incubation period of prions is unknonw, but it is speculated that the disease may develop many years (up to 30-50 years) after initial exposure. However, these reports remain controversial.

Pathogenesis

• The CJD prion promotes refolding of the native proteins into the diseased state.
• The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells.
• This mass of misfolded proteins disrupts cell function and causes cell death.
• Once the prion is transmitted, the defective proteins invade the brain and are produced in a self-sustaining feedback loop, causing exponential spread of the prion.

Mutations

• Mutations in the gene responsible for the production of prion protein can cause misfolding of the alpha helical regions into beta pleated sheets.
• This change in the conformation disables the ability of the protein to undergo digestion.
• Individuals may also acquire CJD genetically through the mutation occurring PRNP gene.

Pathology

Gross Pathology

• On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue.

Microscopic Pathology

• CJD is associated with the build-up of abnormal prion proteins.

• The following microscopic findings may be present in CJD:
  • Presence of florid plaques, defined as round, packed deposits of abnormal prion protein (in variant CJD)
  • Spongiform changes
  • Neuronal loss
  • Astrocyte proliferation
  • Deposition of prion protein throughout the brain

Spongiform changes in brain in CJD

References

Template:WikiDoc Sources