Mechanisms of cell death in cholinergic basal forebrain neurons in chronic alcoholics

Abstract

Tau immunoreactivity was examined in post mortem tissue from patients in three groups: neurologically-asymptomatic and neuropathologically normal alcoholics, alcoholics with Wernicke's Encephalopathy (WE) and age matched non-alcoholic controls. Tau-positive granular and fibrillary inclusions were frequently observed within the magnocellular neurons of the cholinergic nucleus basalis, within occasional nucleus basalis neurons in non-WE alcoholics, but not in controls. Tau immunoreactivity was not however observed in cortical, brainstem, diencephalic or non-cholinergic forebrain structures. Peroxidase activity was also examined within the nucleus basalis using diaminobenzidine as an indicator. The majority of neurons in the basal forebrain showed increased peroxidase activity in all WE alcoholics and in some nucleus basalis neurons of non-WE alcoholics, but was rarely seen in controls. Neighboring astrocytes also showed increased peroxidase activity. These results suggest a link between peroxidase activity and the abnormal accumulation of phosphorylated tau. The presence of tau in the nucleus basalis of alcoholics with WE suggests a thiamine-dependent mechanism in tau accumulation and cell death in the cholinergic basal forebrain.