A CONFOCAL MICROSCOPIC ANALYSIS OF GALANINERGIC HYPERINNERVATION OF CHOLINERGIC BASAL FOREBRAIN NEURONS IN ALZHEIMERS-DISEASE

The galanin (GAL) containing peptide fiber system innervates the basal forebrain and has been shown to hyperinnervate remaining cholinergic neurons in Alzheimer's disease (AD). GAL modulates the release of acet ylcholine and, therefore, may depress this neurotransmitter in survivi ng cholinergic basal forebrain (CBF) neurons in AD. The aim of this st udy was to identify putative synaptic contacts between GAL immunoreact ive processes and CBF neurons and evaluate whether these processes hyp ertrophy in AD patients. We observed by confocal laser microscopy a hy perinnervation of GAL-containing fibers in both AD and Parkinson's dis ease patients with concurrent AD (PD/AD). Galaninergic fibers were oft en seen in direct apposition to remaining CBF neurons and enwrapped ch olinergic cell soma and dendrites. Our results demonstrate that GAL-co ntaining fibers are in direct apposition to CBF neurons in normal-aged humans and that this phenotype is enhanced in AD and PD/AD, suggestin g that direct synaptic contacts occur between GAL-containing fibers an d CBF neurons. Because GAL can modulate acetylcholine release from cho linergic neurons, hyperinnervation of GAL fibers in AD and PD/AD patie nts may further decrease release of acetylcholine from remaining CBF n eurons. We propose that therapies based solely on acetylcholinesterase inhibitors may be insufficient to effectively increase cortical level s of acetylcholine.