A novel erythroid-specific marker of transmissible spongiform encephalopathies

Transmissible spongiform encephalopathies (TSE) are a group of invariably f atal neurodegenerative diseases and include scrapie in sheep, bovine spongi form encephalopathy (BSE) in cattle, chronic wasting disease in deer and el k, and Kuru disease, Creutzfeldt-Jakob disease (CJD) and variant CID in hum ans(1,2). The pathological effects of disease occur predominantly in the CN S (central nervous system), where common hallmarks include vacuolation, gli osis, accumulation of a protease-resistant, abnormally folded isoform of th e prion protein (PrPSc) and neuronal cell death(1,2). Lack of understanding of the molecular mechanisms underlying disease pathogenesis, particularly in non-CNS tissues, means that there are currently no effective strategies for early diagnosis or therapeutic intervention of TSEs. Here we report the first identification of a molecular marker that is easily detectable in re adily accessible tissues. We demonstrate that a dramatic: decrease in expre ssion of a transcript specific to erythroid lineage cells is a common featu re of TSEs. Our findings indicate a previously unrecognized role for involv ement of the erythroid lineage in the etiology of TSE pathogenesis and shou ld provide a new focus for research into diagnostic and therapeutic strateg ies.