Table 1. Secondary accumulation of gangliosides in diseases with neurological impairment.

Table 1 summarizes the alterations in glycosphingolipid metabolism leading to secondary ganglioside accumulation in several diseases characterized by neurological impairment, with or without impairment of lysosomal function.

Disease	Lysosomal involvement	Effect on gangliosides	References
Niemann Pick type A	yes	GM3 and GM2 accumulation	Rodriguez-Lafrasse et al., 1999; Scandroglio et al., 2008; Buccinna et al., 2009
Niemann Pick type C	yes	GM3 and GM2 accumulation	Siegel and Walkley, 1994; Sleat et al., 2004
Mucopolysaccharidosis	yes	GM3 and/or GM2 accumulation	Siegel and Walkley, 1994; Constantopoulos and Dekaban,1977; Constantopoulos et al., 1978; Constantopoulos et al., 1980; Liour et al., 2001
α-mannosidosis	yes	GM3 and GM2 accumulation	Siegel and Walkley, 1994, Goodman et al.,1991
Alzheimer’s disease	no	Reduced ganglioside concentration in several brain areas and altered ratios of a- series to b-series gangliosides Elevated levels of simpler gangliosides (GM3 and GM2)	Brooksbank and McGovern, 1989; Crino et al., 1989; Kalanj et al., 1991; Kracun et al., 1991; Kracun et al., 1992; Svennerholm et al., 1994 Kracun et al., 1992; Barrier et al., 2007)
Huntington’s disease	no	Reduced ganglioside concentration in erythrocytes, striatum and caudate Abnormal expression of glycosyltranserase genes Increased GD3 levels	Wherrett and Brown, 1969; Higatsberger et al., 1981; Desplats et al., 2007 Desplats et al., 2007 Desplats et al., 2007
Prion diseases	no	Reduced ganglioside content with a shift from complex to simpler species (GM3, GD3, GD2) Alterations in the long-chain base composition of gangliosides	Yu et al., 1974; Tamai et al., 1979; Ando et al., 1984; Di Martino et al., 1993; Ohtani et al., 1996 Di Martino et al., 1993
Severe malignant autosomal recessive osteopetrosis	uncertain	Accumulation of GM3 and GM2, no changes in lysosomal glycohydrolases	Prinetti et al., 2009