No abstract

No abstract

Forty different brain samples, consisting of neocortical, archicortical, and paleocortical areas; telencephalic, diencephalic, and mesencephalic subcortical nuclei; and the cerebellum as well as some of the corresponding white matter bundles were analyzed with respect to total content of ganglioside-sialic acid and the ganglioside pattern. The total content of gangliosides seems to depend mainly on the proportions of gray and white matter. Thus, neocortical areas, which are rich in gray matter, have a four- to fivefold higher ganglioside content (per milligram of protein) than white matter-rich samples such as optic chiasm, capsula interna, or corpus callosum. White matter-rich regions, although very heterogeneous in ganglioside composition, are further characterized by appreciable amounts of the myelin-enriched GM4. In the neocortex a remarkable degree of regional pattern differences was revealed. In the frontal and parietal areas there is a moderate, and in the temporal region a strong preponderance of sialic acid bound to gangliosides of the a-pathway (GD1a, GM1). In contrast, the occipital cortex favors the b-pathway of ganglioside synthesis (GQ1b, GT1b, GD1b). A predominance of "b-gangliosides" was found in all structures that are related to the visual system (optic chiasm, pulvinar-thalamus, superior colliculi, visual cortex) as well as in the cerebellum and the nucleus ruber. All diencephalic nuclei tend to favor slightly "b-gangliosides," while the mesencephalic nuclei are very heterogeneous in their ganglioside composition. A preponderance of "a-gangliosides" was found in the periamygdalar cortex, putamen, inferior colliculi, substantia nigra, frontal white matter, internal capsule, globus pallidus, basal nucleus of Meynert, and corpus callosum as well as in the frontal, parietal, and temporal cortices. An exceptional predominance of GM1 and GD1a was revealed for the hippocampal archicortex and the amygdala, suggesting a possible functional correlation to glutaminergic synaptic transmission.

Previous studies suggested the possibility of accelerated lysosomal degradation of brain gangliosides in Alzheimer's disease (AD). As AD pathology affects both neural and nonneural tissues, the aim of this study was to determine possible changes of glycosphingolipid metabolism in available peripheral cells in AD and Down's syndrome (DS). The activities of several lysosomal enzymes involved in catabolism of gangliosides and sulfatides were measured in leukocytes from subjects with dementia of the Alzheimer type, DS, and age-matched controls, by fluorimetry and spectrophotometry using specific substrates. The results showed a statistically significant increase of ␤ -galactosidase activity in both dementia of the Alzheimer type and DS leukocytes when compared with age-matched controls ( p Ͻ .01 and p Ͻ .05, respectively; Student's t test). Not significantly increased activities of ␤ -galactosidase, ␤ -hexosaminidase, ␤ -hexosaminidase A, and slightly decreased activity of arylsulfatase A were observed in control leukocytes with aging. Our results indicate that a metabolic dysfunction and the acceleration of at least some lysosomal catabolic pathways are present in AD and DS nonneural cells. ć LZHEIMER'S disease (AD) is a neurodegenerative disorder of unknown etiology. The hypothesis of disturbed glycosphingolipid (GSL) metabolism in AD is based on several facts. First, previous studies showed changes in content and composition of brain gangliosides in Alzheimer's disease (1), and they suggested the possibility of accelerated lysosomal degradation of GSLs in AD brains (2). Second, numerous studies have shown that pathologic processes and biochemical disturbances in AD affect not only neural but also nonneural tissues (3-10). Third, the majority of biochemical disorders in neural and nonneural tissue result in seriously damaged structure, function, and fluidity of cell membranes (11-15). Finally, gangliosidesGSLs containing sialic acids-are incorporated in all animal cell membranes, with the highest content, variety, and specific regional distribution found in the human brain tissue. As important membrane constituents, GSLs confer to its structural rigidity and are also (themselves or as intermediate metabolites) key players in processes such as cell growth, proliferation, differentiation, cell recognition, and apoptosis (16-20).Down's syndrome (DS) is used as a comparative model for the study of AD: the same clinical symptoms of dementia and the neuropathological hallmarks characteristic of AD are present in older DS individuals (21). Also, similar biochemical disorders have been observed in both AD and DS nonneural tissues (7).The aim of this study was to determine possible changes of GSL metabolism in available peripheral cells derived from subjects with a clinical diagnosis of dementia of the Alzheimer type (DAT) and DS. M ETHODS SubjectsBlood samples were collected at the Department for Neurology, University Hospital "Sestre milosrdnice" in Zagreb, from 19 patients (7 men and 12 women, age range 47-86 years; Tab...

No abstract