Sequential histochemical studies of neuronal lipofuscin in human cerebral cortex from the first to the ninth decade of life

The typical and most consistent physico-histochemical properties of lipofuscin granules, such as autofluorescence, sudanophilia, acid-fastness, PAS-reactivity, and lectin reactivities for diverse saccharide moieties have been generally detected in tissue specimens of old humans and animals. The purpose of this study was, therefore, to explore possible sequential variations of each of these properties in cortical neurons of the left cerebral temporo-parietal areas from individuals dying from the first to the ninth decade. Autofluorescence was studied with an ad hoc equipped microscope, sudanophilia was evaluated by Oil-red-O (ORO) staining, acid-fastness by long Ziehl-Nielsen reagent, PAS reactivity by the periodic-acid-Schiff reagent before and after diastase treatment, and the saccharide moieties by the use of a commercial kit of seven different biotinylated lectins. In the specimen from a 5-year-old child, lipofuscin granules were detected in less than 5% of the cortical neurons, but these granules already showed golden-yellow autofluorescence, sudanophilia, acid-fastness and PAS-reactivity. From the second to the ninth decade of life, perikaryal lipofuscin granules were found in practically all cortical neurons with apparent agewise increases in the intensity of sudanophilia and PAS-reactivity, but with variable acid-fastness expression. Surprisingly, however, no saccharide residues were detected by lectin histochemistry before the fifth decade of life. First detected saccharide was mannose in specimens from the fifth decade of life, and at later decades acetyl galactosamine, sialic acid and lactose were also found. Although, the reasons for the absence of lipofuscin affinity for the seven lectins used in this study in the cortical neurons of young and middle-aged individuals are presently unknown, these unexpected findings suggested important evolutionary changes of biogenesis and composition of the age-pigment. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.