Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?

Area of Science:

• Neuroscience
• Infectious Diseases
• Prion Biology

Background:

• High prevalence of healthy variant Creutzfeldt-Jakob Disease (v-CJD) carriers suggests potential for wider disease spread.
• Blood from v-CJD exposed individuals may be infectious, posing a public health concern.

Purpose of the Study:

• To investigate the transmissibility of v-CJD via blood transfusion in animal models.
• To identify and characterize novel neurological syndromes associated with v-CJD transmission.

Main Methods:

• Experimental blood transfusion from v-CJD exposed individuals (human and animal) to macaques and mice.
• Confirmation of prion etiology through transmission experiments.
• Neurological and pathological examination of recipient animals.

Main Results:

• v-CJD was confirmed as transmissible through blood transfusion in both macaques and mice.
• Unexpected, transmissible neurological syndromes were observed, escaping classical prion diagnosis due to undetectable abnormal PrP.
• Macaques developed a novel myelopathic syndrome affecting the spinal cord, brainstem, and optical tract without encephalon involvement.

Conclusions:

• The spectrum of human prion diseases may extend beyond phenotypes associated with detectable abnormal PrP.
• Prion diseases can manifest as spinal cord disorders, challenging current diagnostic approaches.
• Further research is needed to understand and diagnose these novel prion-related neurological syndromes.