Fig. 1

Deficits in GCase Activity in Inferior Frontal Gyrus from Patients with FTD-GRN. Lysates from inferior frontal gyrus of controls and FTD-GRN patients were analyzed for activity of sphingolipid-metabolizing enzymes. a, Simplified diagram of metabolism of gangliosides, with a summary of observed phenotypes in FTD-GRN cases. Lipids are shown in black, with the enzymes that metabolize each lipid shown in blue. GM1, 2, and 3 = GM1, 2, and 3 ganglioside, β-Gal = β-galactosidase, β-Hex = β-Hexosaminidase, HexA = β-Hexosaminidase A, GLA = α-galactosidase A, GCase = β-glucocerebrosidase, Neu = neuraminidase (activity not measured in this study). b–f, Enzymatic activity in FTD-GRN patient brains as measured by fluorogenic assays for b, β-Gal, c, β-Hex, d, HexA, which was increased (* = t test, p = 0.0474), e, GLA, and f, GCase, which was decreased (** = t test, p = 0.0015). n = 5 controls, 7 FTD-GRN