Compartmental protein expression of Tau, GSK-3beta and TrkA in cholinergic neurons of aged rats.

During aging basal forebrain cholinergic neurons (BFCNs) degenerate, and we hypothesize this to be the result of a degeneration of the cytoskeleton. As a corollary, retrograde transport of the complex of nerve growth factor (NGF) and its activated receptor phospho-TrkA (P-TrkA) is impaired. Using immunocytochemistry, we here compare young and aged rat brains in their subcellular localization of NGF and P-TrkA in relation to the compartmentalization of phosphorylation-dependent tau protein isoforms. Despite lower P-TrkA immunoreactivity in cortex and hippocampus of aged rats, NGF immunoreactivity was not altered in these areas, but was significantly lower in aged basal forebrain. In young animals, expression of tau isoforms and glycogen synthase kinase-3beta (GSK-3beta) was restricted to neuritic structures in cortex, hippocampus, and basal forebrain. In contrast, tau and GSK-3beta labeling was confined to cell bodies in aged rats. Since a somatic localization of phospho-tau is indicative of cytoskeletal breakdown, we suggest this to be the mechanism the breakdown of trophic support in aging BFCNs.