Colocalization of Lysosomal Hydrolase and β-Amyloid in Diffuse Plaques of the Cerebellum and Striatum in Alzheimerʼs Disease and Downʼs Syndrome

Neuroglia in the inferior olivary nucleus during normal aging and Alzheimer's disease

“…Furthermore, the presence of a low amount of amyloid accumulation in PO is a common finding, with an exacerbation in the mutation cases [41]. These findings concerning tau and amyloid pathology in PO are intriguing since the lysosomal system has been suggested to be involved in pathogenic mechanism of both tau and amyloid pathways [44][45][46][47][48]. It could happen that diverse morphological phenotypes, with regional and cellular differences, are exposed to the same underlying pathogenic mechanism.…”

Thematic Review Series: Sphingolipids. Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease—a review

“…This significant decrease in the serum sialyltransferase activity may prove to be a useful early biochemical marker of neurodegeneration and may provide an indication of the underlying cellular events that occur during the process of nerve cell death in AD (46). Cataldo et al (47) found that lysosomal hydrolases, cathepsin D, and b-hexosaminidase A were colocalized with Ab in a subgroup of diffuse plaques in the cerebellum and striatum of individuals with AD or DS. It is suggested that the activities of several lysosomal enzymes involved in catabolism of gangliosides may be taken as a peripheral hallmark of AD or DS patients.…”

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

“…This hypothesis was supported by immunohistochemical studies of Cataldo and colleagues, showing both abnormal distribution and colocalization of several lysosomal hydrolases and proteases (β-hexosaminidase A, α-glucosidase, catepsin D) with β-amyloid in diffuse plaques in cerebellum and striatum in AD and Down's syndrome (DS) brain tissue [2] and [3]. A documented increased expression of lysosomal hydrolases in neuronal populations affected by amyloid pathology was explained as a proof for up-regulation of endosomal-lysosomal systems and was proposed to be an early marker of metabolic dysfunction related to primary AD etiopathogenesis [2] and [3]. It was a logical step further to analyze glycosphingolipid metabolism in peripheral cells.…”

“…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 Kračun et al in 1990 and1992 [13] and [14]. This hypothesis was supported by immunohistochemical studies of Cataldo and colleagues, showing both abnormal distribution and colocalization of several lysosomal hydrolases and proteases (β-hexosaminidase A, α-glucosidase, catepsin D) with β-amyloid in diffuse plaques in cerebellum and striatum in AD and Down's syndrome (DS) brain tissue [2] and [3]. A documented increased expression of lysosomal hydrolases in neuronal populations affected by amyloid pathology was explained as a proof for up-regulation of endosomal-lysosomal systems and was proposed to be an early marker of metabolic dysfunction related to primary AD etiopathogenesis [2] and [3].…”