Calbindin-D28K, Parvalbumin and Calretinin in Young and Aged Human Locus Coeruleus

Abstract Certain neuronal populations, including the cholinergic neurons of the basal forebrain (BFCN) and the noradrenergic neurons of the locus coeruleus (LC), are selectively vulnerable to pathology and loss early in the course of aging and Alzheimer’s disease (AD). We have shown that BFCN in the human brain show a substantial loss of the calcium binding protein, calbindin-D28K (CB), over the course of normal aging, which is associated with formation of neurofibrillary tangles and loss of BFCN in AD. The purpose of this study was to determine if, similar to the BFCN, LC neurons contain CB or the other two ubiquitous calcium binding proteins (CBP) parvalbumin and calretinin, and if so, whether these proteins display an age-related loss from LC neurons. Immunostaining for CBPs and tyrosine hydroxylase (TH), a marker of catecholaminergic neurons, were used in sections from the LC of young and aged human brains. Parvalbumin and calretinin immunoreactivities were completely absent from human LC neurons. A subpopulation of LC neurons (∼10%) contained CB immunoreactivity. Quantitative analysis using sections stained concurrently for visualization of CB and TH revealed no age-related loss of the former from the LC neurons. These findings indicate that, unlike the BFCN, age-related loss of CB does not figure prominently in the selective vulnerability of LC neurons to tangle formation and degeneration in AD.