Changes in Brain Cholinesterases in Senile Dementia of Alzheimer Type

Abstract

Acetyl- and butyryl-cholinesterase activities have been measured biochemically in normal brain tissue, in senile dementia of Alzheimer type and in mental disorders without Alzheimer-type abnormalities. Acetylcholinesterase was significantly reduced and butyrylcholinesterase significantly increased, compared with the normal, in the hippocampus and temporal cortex of the Alzheimer cases. No significant enzyme changes were seen in the other diseases investigated including multi-infarct dementia, schizophrenia and depression. There was no correlation between age and acetylcholinesterase activity, but a significant positive correlation between the butyrylcholinesterase activities with increasing age (60-90 years) was found in the hippocampus. The possible connection between cholinergic system pathology and these cholinesterase abnormalities in Alzheimer dementia is discussed.

Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors

“…However, as AD progresses, the activity of AChE decreases, while that of BuChE significantly increases in the hippocampus and temporal cortex [12].…”

Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:

“…In contrast, rivastigmine acts differently from donepezil and galantamine in targeting both AChE and BuChE. 22 Although BuChE represents only 10% of total ChE activity in the temporal cortex of the healthy human brain, 27 recent results using sensitive histochemical techniques indicate that the enzyme is capable of hydrolyzing ACh and plays a greater role in normal cholinergic transmission than previously thought. 28 The importance of BuChE in cholinergic neurotransmission is likely to increase in AD because as the disease progresses, AChE activity decreases by up to 45%, and BuChE activity increases by 40% to 90%.…”

“…28 The importance of BuChE in cholinergic neurotransmission is likely to increase in AD because as the disease progresses, AChE activity decreases by up to 45%, and BuChE activity increases by 40% to 90%. 27,29 Results with rivastigmine show that cognitive improvements (measured using the computerized neuropsychologic test battery) correlate independently with the inhibition of AChE and BuChE in the cerebrospinal fluid of AD patients, 30 suggesting that inhibition of both enzymes is a highly desirable feature of AD therapy.…”

“…27,29 The ratio of BuChE:AChE may change from 0.6 to as high as 11.0, 77 which may alter the normally supportive role of BuChE in the hydrolysis of excess ACh. As a dual inhibitor of both AChE and BuChE, rivastigmine may provide maximum preservation of ACh levels independent of the changing contributions of AChE and BuChE to ACh hydrolysis as the disease progresses.…”

Tetrahydrofurobenzofuran cymserine, a potent butyrylcholinesterase inhibitor and experimental Alzheimer drug candidate, enzyme kinetic analysis

“…In the temporal cortex of normal human brain, for example AChE accounts for some 90% of ChE activity, with BuChE accounting for the remainder (Perry et al 1978). However, whereas AChE is localized mainly to neurons, BuChE is associated primarily with glial cells as well as neurons and, in specific brain areas, nuclei of BuChE-rich neurons and neural tracts that utilize BuChE alone appear to exist .…”