Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of these PrP aggregates is important both in attempting to the elucidate of the pathogenesis of prion disease and in the development of treatments designed to prevent or inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein aggregates. Mathematical models suggest that if aggregation/disaggregation or surface diffusion is the predominant factor, the size frequency distribution of the resulting protein aggregates in the brain should be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different types of PrP deposit, viz., the diffuse and florid-type PrP deposits in patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse plaques were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of plaque deviated significantly from a log-normal model in all brain areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid plaques. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse plaques. These results may be useful in the design of treatments to inhibit the development of protein aggregates in vCJD.
|Title of host publication||Creutzfeldt-Jakob disease: New Research|
|Editors||Mic J. Stones|
|Place of Publication||New York (US)|
|Publisher||Nova Biomedical Press|
|Number of pages||18|
|Publication status||Published - 13 Sep 2007|
- variant Creutzfeldt-Jakob disease
- prion protein aggregate
- size distribution
- log-normal distribution
- florid plaque
- diffuse plaque
- Alzheimer’s disease
Armstrong, R. A. (2007). Modelling the growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease. In M. J. Stones (Ed.), Creutzfeldt-Jakob disease: New Research (pp. 109-126). Nova Biomedical Press.