Early Appearance and Regional Differences in Intraneuronal and Extraneuronal Lipofuscin Accumulation with Age in the Brain of a Nonhuman Primate (Macaca mulatta)
The aims of this study were to examine the earliest onset and age-dependent accumulation of lipofuscin pigment in different regions of the brain in the rhesus monkey. Fifty-two subjects, ranging from 1 day to 22 years were examined. Tissue samples from 17 areas comprising 6 regions were fixed by intracardiac perfusion or immersion, embedded in Paraplast, sectioned at 6 μ, and examined for lipofuscin under blue-light fluorescence in unstained sections, or by PAS and Nile blue in stained sections. Lipofuscin was examined in 2 neocortical laminae, 1 hippocampal, 2 cerebellar areas, and 11 subcortical nuclei. Maximum reported life-span of the rhesus monkey extended to 32 years. The earliest appearance of lipofuscin occurred in the inferior olive in a 3-mo.-old infant. Aggregation of dispersed pigment granules into congregated forms and increasingly brighter yellow-orange fluorescence occurred progressively from 4.0 to 9.5 and 19.5 years. The rank order of regional lipofuscin accumulation from lowest to highest was: cerebellum, neocortex, pons, midbrain, hippocampus, and medulla. Differences in lipofuscin among the 17 areas became significantly greater from 5 homogeneous subsets at 4.0 to 7 at 9.5 and 10 at 19.5 years. Distinct age and regional differences in lipofuscin accumulation also occurred in glia and neuropil. The most noteworthy observations were the early appearance, gradual but dramatic age-dependent and differential-regional accumulation of lipofuscin in the primate brain.