Study on novel cholinergic pathways in the brain of patients with Alzheimer's disease

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A splice variant of choline acetyltransferase mRNA has recently been identified in the pterygopalatine ganglion of rat. An antibody against this variant protein (designated pChAT) was demonstrated to immunolabel peripheral cholinergic neurons. In the present study, we investigated the expression of pChAT in rat brain. Among the brain regions examined, magnocellular neurons in the tuberomammillary nucleus of the posterior hypothalamus were immunohistochemically labelled with anti-pChAT antibody, while no immunolabelling was detected in cholinergic neurons in the basal forebrain or striatum. Long axonal projections of pChAT-positive cells in the tuberomammillary nucleus were shown by retrograde labelling of these cells after injection of cholera-toxin B subunit into the cerebral cortex.This study demonstrates that a splice variant of choline acetyltransferase is expressed in the tuberomammillary nucleus. The results raise the possibility that some of the known diverse projection areas of this nucleus may have a cholinergic component.So far, however, no pChAT was detected in the brain of Alzheimer's disease. ThecDNA analysis of human peripheral ganglia revealed a novel type of ChAT variant which is suspected to be yield by a different splicing mechanis from rat. Further studies will be needed to clarify human pChAT.