ABSTRACT
References 435
The demonstration of deficits in choline acetyltransferase (ChAT) activity in patients dying with Alzheimer’s disease (AD) (Bowen et al., 1976; Davies and Maloney, 1976), together with human anticholinergic drug studies (Drachman and Leavitt, 1974), led to the eventual development of cholinesterase inhibitors (ChEIs) for the symptomatic treatment of AD. Present neurochemical investigations of this system attempt to understand how early the cholinergic deficit develops and the extent to which it occurs in mild cognitive impairment (MCI). In addition, recognition of the role of the glutamatergic system in learning and memory has prompted study of biochemical markers of the major excitatory neurotransmitter system. Anatomical studies suggest interconnectivity between glutamatergic and cholinergic systems but their exact role in AD still requires further elucidation. Just as cholinergic and glutamatergic disruption may be additive in contributing to cognitive and behavioural symptoms of dementia, so pharmacological replacement therapy may be synergistic (Francis et al., 1993; Francis 2005).
