LOCUS-COERULEUS CELL LOSS IN THE AGING HUMAN BRAIN - A NONRANDOM 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 immunohistoc hemical staining for the catecholaminergic enzyme tyrosine hydroxylase and/or by neuromelanin pigment content. Cell locations were mapped, u sing 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 t he neurons with aging. In brains less than 25 years of age there were many fewer pigment-containing neurons than tyrosine hydroxylase-contai ning neurons; however, by the fifth decade the number of cells identif ied by the two markers was comparable. From the first to the tenth dec ade 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 t yrosine hydroxylase immunostained cells (mean +/- standard error of th e mean) on one side of the brain; in seven cases from ''old'' individu als (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'' t here 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 grea ter extent than do the caudal, spinal cord-projecting neurons. The pat tern of cell loss that occurs with normal aging is similar to that fou nd in Alzheimer's disease and in Down's syndrome. (C) 1995 Wiley-Liss, Inc.