J. Inher. Metab. Dis. 16 (1993) 280-283 © SSIEM and KluwerAcademicPublishers. Printed in the Netherlands NCL Symposium Ceroid, Lipofuscin and the Ceroid- lipofuscinoses (Batten Disease) R. D. JOLLY, R. R. DALEFIELDand D. N. PALMER Department of Veterinary Pathology and Public Health, Massey University, Palmerston North, New Zealand LIPOPIGMENTS AND CEROID-LIPOFUSCINOSIS The term lipopigment is a general one given to yellow-brown pigments that stain with lipid stains and fluoresce under UV lights. Their terminology is confused and there is a general lack of information concerning their biogenesis and significance. In the 1970s there developed a perception that abnormal lipid peroxidation with formation of Schiff-base-protein polymers was the unifying feature that linked these pigments. This paper discusses three lipopigments with known associations and demonstrates that lipid peroxidation is not a unifying feature. The prototype pigment is lipofuscin (age pigment) first described 150 years ago. Because of its ubiquity in cells of aged individuals, accumulation has been perceived as a normal phenomenon. However, it is questionable whether lipofuscin is an age pigment resulting from a genetic programme associated with the ageing process or the result of cumulative environmental influences. In contrast to lipofuscin, the term ceroid has been used to describe any pathological lipopigment, including the lipopigment of ceroid-lipofuscinosis. Its continued use should be limited to those pigments where there is observational or epidemiological evidence of degeneration and/or peroxidation of lipid (Jolly and Dalefield 1990). Despite abundant evidence for these features being involved in disease characterized by formation of ceroid, its putative Schiff-base-protein polymeric nature is based merely on theoretical expectations and not chemical analysis. A similar putative composition and biogenesis for age pigment is based entirely on analogy and theoretical considerations. We have questioned this by isolation and analysis of lipofuscin from the thyroid of variously aged horses. Results, which are to be published in detail elsewhere, are summarized as follows: (1) Lipofuscin accumulated relative to age only up to maturity at 5 years. Thereafter there was no quantitative relationship with age. (2) In horses under 5 years, heavy pigmentation of individual follicles was associated with one of several abnormalities of colloid, implying an association with abnormal cell function. (3) Isolated pigment could mostly be solubilized and analysed, although technical difficulties were encountered in extracting carbohydrate quantitatively. The chemical composition of this pigment was variable between horses but its general composition by weight was as follows: protein 30%; dolichol 6.4%; cholesterol 6.3%; phospholipid 1.3%; DNA 2.4%; metals 1.8%; halides (iodide) 5.1%; carbohydrate up to 36%. Most of the 280