Ganglioside catabolism is altered in fibroblasts and leukocytes from Alzheimer's disease patients

Abstract

0 d skin fibroblasts) derived from patients with diagnosis of lzheimer’s disease (AD). The authors suggest that found iochemical alterations could serve as a peripheral hallmark f the disease. This paper, amongst many others, presents dditional evidence supporting the theory that AD is either a ystemic disease or at least has numerous systemic implicaions, which may be recognized and used for diagnostic puroses. In available literature there have been only a few data eferring to glycosphingolipid metabolism in AD peripheral ells. However, it has to be pointed out that the observations n glycosphingolipid metabolic alterations not only in AD ut also in Down’s syndrome (DS) peripheral tissues have een previously published by other groups [9,17], in addiion to the paper by Pitto et al. [19]. The biological roles of glycosphingolipids have been xtensively studied and their involvements in key cellular However, a tempting speculation that observed biochemical alterations of gangliosides are due to the accelerated lysosomal degradation of gangliosides in AD brain tissue was in fact proposed by Kracun et al. in 1990 and 1992 [13,14]. This hypothesis was supported by immunohistochemical studies of Cataldo and colleagues, showing both abnormal distribution and colocalization of several lysosomal hydrolases and proteases ( -hexosaminidase A, -glucosidase, catepsin D) with -amyloid in diffuse plaques in cerebellum and striatum in AD and Down’s syndrome (DS) brain tissue [2,3]. A documented increased expression of lysosomal hydrolases in neuronal populations affected by amyloid pathology was explained as a proof for up-regulation of endosomallysosomal systems and was proposed to be an early marker of metabolic dysfunction related to primary AD etiopathogenesis [2,3]. It was a logical step further to analyze glyvents as well as their particularly important functions in nimal brain tissue are well known [8,15,20,24]. The idea hat there are alterations in glycosphingolipid metabolism in lzheimer’s disease arose from biochemical studies of brain angliosides pattern [1,11,20]. These studies established that cosphingolipid metabolism in peripheral cells. In 1994 and 1995, Maguire and colleagues showed decreased activity of GSL biosynthetic enzymes (sialyltransferases) in serum [16] and brain tissue [17] in AD and DS as compared with control samples. In our study published in 2002, the activity of several e g a l D n l c i pecific changes of content and composition of brain ganglioides may serve as stage specific markers of brain developent and aging [12,21]. Also, it was shown that ganglioside attern is altered in AD brains [5,13,14]. Specific changes n content and composition of gangliosides and other memrane lipids in AD brain regions were documented by several