A 43-kDa TDP-43 species is present in aggregates associated with frontotemporal lobar degeneration.

The transactive response DNA-binding protein (TDP-43) is a major component of the abnormal intracellular inclusions that occur in two common neurodegenerative diseases of humans: (1) a subtype of frontotemporal lobar degeneration and (2) amyotrophic lateral sclerosis. Genetics, experiments in cultured cells and animals, and analogy with other neurodegenerative diseases indicate that the process of TDP-43 aggregation is fundamental to the pathogenesis of these 2 diseases, but the process by which this aggregation occurs is not understood. Biochemical fractionation has revealed truncated, phosphorylated and ubiquitinated forms of TDP-43 in a detergent-insoluble fraction from diseased CNS tissue, while these forms are absent from controls.

Reversible cerebral vasoconstriction syndrome 3 months after blood transfusion.

Reversible cerebral vasoconstriction syndrome is characterized by the prolonged but reversible constriction of cerebral arteries accompanied by a sudden onset of severe headache, and is sometimes complicated by subarachnoid hemorrhage or cerebral infarction. It is associated with various clinical conditions and treatments, although the precise pathophysiology is not understood. In particular, several cases of this syndrome have been described to occur in middle-aged women within 1 week of a blood transfusion.

Transmission of elk and deer prions to transgenic mice.

Chronic wasting disease (CWD) is a fatal prion disease in deer and elk. Unique among the prion diseases, it is transmitted among captive and free-ranging animals. To facilitate studies of the biology of CWD prions, we generated five lines of transgenic (Tg) mice expressing prion protein (PrP) from Rocky Mountain elk (Cervus elaphus nelsoni), denoted Tg(ElkPrP), and two lines of Tg mice expressing PrP common to white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus), denoted Tg(DePrP).

Bovine spongiform encephalopathy, chronic wasting disease, scrapie, and the threat to humans from prion disease epizootics.

Ongoing endemics and epidemics of prion disease afflict several species of ruminants regularly consumed by humans. Bovine spongiform encephalopathy (BSE) is epidemic in British cattle, and is now found in the cattle of more than 20 countries. A large, and apparently growing, epidemic of chronic wasting disease plagues deer and elk in North America.

Prions in skeletal muscle.

Considerable evidence argues that consumption of beef products from cattle infected with bovine spongiform encephalopathy (BSE) prions causes new variant Creutzfeldt-Jakob disease. In an effort to prevent new variant Creutzfeldt-Jakob disease, certain "specified offals," including neural and lymphatic tissues, thought to contain high titers of prions have been excluded from foods destined for human consumption [Phillips, N. A.