NONNEURAL MARKERS IN ALZHEIMER-DISEASE

Nonneural tissues are now widely used to search for abnormalities in genes as well as for other markers of dementia of the Alzheimer type (DAT). Studies of nonneural tissues can experimentally circumvent problems inherent in the study of autopsy brain, but to be meaningful, abnormalities identified in the periphery must be correlated with abnormalities in the brain, which is the tissue of clinical interest. Among the topics in DAT research that can be readily studied in nonneural cells (including tissue cultures) are molecular genetics, amyloid precursor protein formation and metabolism, systemic manifestations of immunological and inflammatory mechanisms, proteolysis, membranes, signal transduction, and mitochondria and metabolism. Although phenomena suggesting the possibility of cytoskeletal abnormalities in nonneural DAT cells have been described, the tau molecules involved in paired helical filament formation are relatively brain-specific. Since the neuropathological diagnosis of DAT depends on recognizing a pattern of changes rather than any single abnormality, it seems unlikely that any one laboratory abnormality in peripheral tissues will correlate precisely with the clinicopathological entity of DAT. However, abnormalities found in nonneural DAT cells that correlate with the existence of similar abnormalities in the brain are likely to be informative about the disease process in the patients in whom they occur.