Research Focus

The Section of Neuropathology research focuses on dementias and their causes, with an emphasis on Transmissible Encephalopathies (TSEs) such as human Creutzfeldt-Jakob disease (CJD), endemic sheep scrapie and “mad cow disease” (BSE and human vCJD). We continues to do fundamental research on neurodegeneration having developed small animal and tissue culture models infected by various human agents including sporadic CJD (sCJD), vCJD, kuru of New Guinea and Asiatic CJD (reviewed in ) Vast differences in the incubation time and regional brain lesions distinguish these different human agents.

Our results emphasize an environmental origin of TSE infectious agents, and the host responses to TSE agents as foreign pathogens. Moreover, it is likely that environmental causes, physiological stresses and several types of infectious agents, underlie more common dementias such as Alzheimer’s Disease (AD) and misfolded proteins such as amyloid. This line of approach deserves investigation, especially in view of major public health issues.

Research
We also do experiments that elucidate the structure of the infectious agent. Our new tissue culture models have revealed virus-like particle arrays (at left) that correspond to isolated infectious brain particles of ~25nm. These arrays were not detectable in uninfected cells. They do not bind PrP antibodies, unlike PrP amyloid, a misfolded form of host PrP that is commonly believed to be the infectious agent or “prion”. We think misfolded PrP is a pathological response to infection. For more information see PMID23633671.

Ultrastructural array of virus-like particles PMID 17267596

For more details see:

http://medicine.yale.edu/lab/manuelidis/particles/index.aspx