CHOLINESTERASES AND THE PATHOLOGY OF ALZHEIMER-DISEASE

Alzheimer disease (AD) is accompanied by a marked loss of acetylcholin esterase (AChE) activity associated with cortical cholinergic axons an d cholinoceptive neurons. Simultaneous with this loss, cholinesterase (ChE) activity emerges in AD cortex in the form of AChE and butyrylcho linesterase activity associated with plaques, tangles, and amyloid ang iopathy. Our observations have shown that the ChEs associated with the pathological lesions of AD (ADChEs) possess different enzymatic prope rties and quite possibly are of a different source as compared with th e ChEs associated with normal neurons and axons. The ADChEs most likel y have noncholinergic functions involved in the pathogenesis of AD. Th e postulated functions include acting as proteases/peptidases, partici pating directly in the amyloidogenic processing of the amyloid precurs or protein, and causing aberrant growth of neuronal processes. The the rapeutic and diagnostic implications of AD ChEs are discus sed.