NEUROGLIAL CHOLINESTERASES IN THE NORMAL BRAIN AND IN ALZHEIMERS-DISEASE - RELATIONSHIP TO PLAQUES, TANGLES, AND PATTERNS OF SELECTIVE VULNERABILITY

Butyrylcholinesterase (BChE) and an altered form of acetylcholinestera se (AChE) accumulate in the plaques and tangles of Alzheimer's disease (AD). The sources for these plaque- and tangle-bound cholinesterases have not been identified. We now report that AChE and BChE activities with pH preferences and inhibitor selectivities identical to those of plaque- and tangle-bound cholinesterases are found in the astrocytes a nd oligodendrocytes of control and AD brains. These glial-type choline sterases are selectively inhibited by indolamines and protease inhibit ors. In control brains glial-type cholinesterases appear confined to t he intracellular space, whereas in patients with AD they decorate plaq ues and tangles as well. In control and AD brains AChE-positive glia a re distributed throughout the cortical layers and subcortical white ma tter, whereas BChE-positive glia reach high densities only in the deep cortical layers and white matter. In non-AD control brains, the ratio of BChE to AChE glia was higher in entorhinal and inferotemporal cort ex, two regions with a high susceptibility to the pathology of AD, tha n in primary somatosensory and visual cortex, two areas with a relativ ely lower susceptibility to the disease process. There were no age-rel ated differences in the density or distribution of cholinesterase-posi tive glia. In comparison with age-matched control specimens, AD brains had a significantly higher density of BChE glia and a lower density o f AChE glia in entorhinal and inferotemporal regions but not in the pr imary somatosensory or visual areas. These results suggest that glia c onstitute a likely source for the cholinesterase activity of plaques a nd tangles and that a high ratio of BChE- to AChE-positive glia may pl ay a permissive or causative role in the neuropathology of AD.