Changes in the Concentration and Composition of Human Brain Gangliosides with Aging

Abstract

Ganglioside content and composition were studied in whole brains from 9 neurologically normal male individuals ranging from 25 to 85 years in age. The content of ganglioside-bound sialic acid decreased from 1,070 to 380 μg/g fresh tissue at 85 years. Ten individual ganglioside fractions were identified on high-performance thin-layer chromatography, seven of which were quantified. With age, ganglioside composition shifted to a more polar pattern due to an increase in the relative concentration of the more polar fractions GQ1b, GT1b and GD1b and a decrease in GD1 a and GM1. Except for GQ1b, the absolute concentration of all gangliosides decreased with age. All changes were more pronounced in younger ages. Results are discussed in relation to structural changes occurring in the aging brain, and the involvement of gangliosides is suggested.

GDNF signaling implemented by GM1 ganglioside; failure in Parkinson's disease and GM1-deficient murine model

“…8), in conjunction with our previous observation of deficient GM1 in DA neurons as well as non-TH + cells in the SNpc of PD subjects (Wu et al, 2012), suggests the intriguing possibility of systemic GM1 deficiency as a predisposing factor in PD. GM1 was shown to decline progressively with age in many regions of human brain and more so its metabolic precursor, GD1a (Svennerholm et al, 1989(Svennerholm et al, , 1994Segler-Stahl et al, 1983;Kracun et al, 1992), thereby approximating over time the partial depletion engineered in the HT mouse (Wu et al, 2012). These findings accord with the idea of age as a primary risk factor for sporadic PD (Collier et al, 2011) and point to the HT mouse as a possibly unique model in reflecting the actual pathophysiology of sporadic PD.…”

Immunohistochemical staining for ganglioside GD1b as a diagnostic and prognostic marker for primary human brain tumors

“…There are changes in the ganglioside composition of normal human brain with development and aging. On the basis of ganglioside sialic acid, the proportion of total ganglioside accounted for by GD1b progressively increases from approximately 10% at birth to 30% in adults (Segler-Stahl et al, 1983;Vanier et al, 1971). This is the inverse of what we found for the relation between .…”

Gangliosides in the brain in adult Down’s syndrome and Alzheimer’s disease

“…During postnatal development in humans, in frontal cortex gray matter there is a decrease in the relative proportion of GDIa and a moderate increase in that of GD1b and GT1b (Vanier et al, 1971). This trend is reported (in the whole brain) to continue through adult life into old age, with a reduction in the relative proportion of GMl as well (Segler-Stahl et al, 1983). Thus the ganglioside pattern in the frontal cortex gray matter of adult DS suggests a relatively underdeveloped pattern of ganglioside formation in DS.…”