Locus coeruleus cell loss in the aging human brain: a non-random process

Quantitative neuroanatomical techniques were used to determine whether with aging there is random or systematic loss of locus coeruleus (LC) neurons in the human brain. The cells were identified by immunohistochemical staining for the catecholaminergic enzyme tyrosine hydroxylase and/or by neuromelanin pigment content. Cell locations were mapped, using computer imaging procedures, in horizontal sections spaced 0.5 to 0.8 mm throughout the rostrocaudal extent of the nucleus in 17 cases, from 1 to 104 years of age. Neuromelanin pigment accumulated within the neurons with aging. In brains less than 25 years of age there were many fewer pigment-containing neurons than tyrosine hydroxylase-containing neurons; however, by the fifth decade the number of cells identified by the two markers was comparable. From the first to the tenth decade of life there is over a 50% loss of LC neurons: in four cases from "young" individuals (1-28 years of age) there were 21,084 +/- 653 tyrosine hydroxylase immunostained cells (mean +/- standard error of the mean) on one side of the brain; in seven cases from "old" individuals (60-82 years of age) there were 16,502 +/- 921 pigment-containing cells; and in the three cases from the "oldest" individuals (103-104 years of age) there were 9,493 +/- 1,236 pigment-containing neurons. In both the "old" and "oldest" groups, compared to the "young," there was significantly greater loss of rostral cells than caudal cells. These data indicate a systematic loss of cells such that the rostral, forebrain-projecting neurons decrease in number with aging to a greater extent than do the caudal, spinal cord-projecting neurons.(ABSTRACT TRUNCATED AT 250 WORDS)