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Title: Cholinesterases in senile dementia of Alzheimer-type
Author: Atack, John Richard
ISNI:       0000 0001 3431 4292
Awarding Body: Newcastle University
Current Institution: University of Newcastle upon Tyne
Date of Award: 1984
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Aspects of cholinesterase distribution were studied in both the central nervous system (CNS) and blood in relation to the- central cholinergic deficit in senile dementia of the Alzheimer type (SDAT). In the MAT neocortex, the - greatest loss of cholinergic-related acetylcholinesterase (AChE) activity was from the upper cortical layers. previous reports indicate that the majority of neuropathological, neurochemical and morphological changes occur in the lower cortical layers, suggesting that the 'cýolinergic deficit in SDAT may not be directly associated with the primary disease processes of this disorder. Furthermore, the study of-AChE molecular forms revealed that in both MAT and demented-Parkinson's disease subjects, the loss of neocortical AChE activity'is due'to a selective loss of the G4 . form of the enzyme. Hence, th6 cortical cholinergic changes in MAT way not'be uniquely associated with Alzheimer-type neuropathological changes. A similar extensive loss of the G4 form of AChE occured in the cholinergically-denervated rat hippocan-pus, indicating that this form is probably associated with cholinergic axonal processes and suggests that these structures degenerate in demented Alzheimer-type an d Parkinsonian cases. In contrast to AChE, ' the., physiological function of butyry1cholinesterase (BChE) is unknown. However, the different intracortical and inter-regional distributions. of AChE and BChE in the CNS, along vith the observation that despite reduced levels of ch6linergic activity in SDAT, BChE was unaltered, all suggest that BChE is not intimately associated with central cholinergic neurotransmission. In the blood, measurement of cholinesterase activity in MAT revealed normal levels of erythrocyte AChE and plasm BChE and elevated plasma AChE activity. The increased plasm AChE activity may reflect increased leakage, through the blood-brain barrier -and/or increased release from degenerating'cholinergic structures. %bilst these results confirm the involvement of the central cholinergic system in SDAT, they also, however, suggest that these chang es may be secondary to more fundamental pathological processes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Enzymes in senility