ABSTRACT
Accumulation of various proteins within cells or in the extracellular space of the central or peripheral nervous system is a feature of many neurodegenerative diseases (Table 1). Indeed, accumulation of b-amyloid protein in senile plaques of Alzheimer’s disease (AD), detected using classic pathological stains and only later identified specifically as containing a specific protein, provided the key to understanding the molecular basis of this disease by providing a target for genetic studies that in turn pointed back to the key role of the amyloid precursor protein. Likewise, the presence of prion protein in the extracellular plaques in transmissible spongiform encephalopathies (TSE) provided a link between a characteristic feature of the pathology in sporadic and inherited forms of TSE and prion gene mutations that were identified in familial forms of TSE (1,2). As in AD, this provided the key to understanding the relationship between altered processing of a specific protein and progressive neurodegeneration in apparently sporadic diseases. In monogenic conditions such as Huntington’s disease and the hereditary ataxias, identification of gene defects led to the finding of accumulations of the gene product (3).
