Evidences path(MESH:D060825) to p(HGNC:CHAT)

Notably, reports that physostigmine and oral anticholinesterases have beneficial effects for patients with AD suggest that the CBF system is somewhat preserved during the progression of dementia, despite well-documented loss of cholinergic biosynthetic machinery (including ChAT and AChE enzyme deficits) in patients with this disease. Interestingly, recent studies have shown that ChAT activity, which results in acetylcholine (ACh) synthesis, is preserved in the neocortex of people with MCI [18,19].

In fact, our group found elevated ChAT activity in the hippocampus and frontal cortex of subjects with MCI [19,20]. These results suggest that cognitive deficits in MCI and early AD are not associated with a reduction in ChAT activity. Moreover, these data indicate that select components of the hippocampal and cortical cholinergic projection system are capable of compensatory and/ or neuroplasticity responses during the early stages of AD.

In MCI, increased hippocampal and frontal cortex ChAT tone may be important for promoting biochemical activity or compensating for neurodegenerative defects, which may delay the transition of these subjects to frank AD. Hippocampal ChAT activity was increased selectively in MCI cases with high Braak scores (Braak III/IV stage) indicative of advanced disease [19], suggesting that a compensatory upregulation of ChAT may be due, at least in part, to the disconnection of glutamatergic entorhinal cortex input to the hippocampus which occurs early in the disease process [21–23]. In this scenario, upregulation of hippocampal ChAT activity may be due to reactive synaptogenesis, the filling in of denervated glutamatergic synapses by cholinergic input arising from the septum [24].

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.