Table 1.
Statistical test describing the figure, data, type of test, and statistical results
| Figure | Description of graph location | Statistical test | Descriptive statistics |
|---|---|---|---|
| 1 B | Percent area of NF (left) and p-α-syn (right) | Nested two-way ANOVA via SPSS Descriptive statistics acquired from GraphPad Prism |
Neurofilament: Interaction: F(1,48) = 1.045, p = 0.3117 Drug treatment: F(1,48) = 0.1011, p = 0.7519 Genotype: F(1,48) = 0.7340, p = 0.3959 p-α-syn: Interaction: F(1,48) = 1.838, p = 0.1815 Drug treatment: F(1,48) = 0.8887, p = 0.3506 Genotype: F(1,48) = 20.29, ****p < 0.0001 |
| 1 D | DQ-BSA | Three-way ANOVA | Interaction: F(1,18) = 3.621, p = 0.0732 Drug treatment × α-syn treatment: F(1,18)= 7.092, *p = 0.0158 Drug treatment × genotype: F(1,18) = 9.580 **p = 0.0062 α-syn treatment × genotype: F(1,18) = 2.512, p = 0.1304 Drug treatment: F(1,18) = 10.41, **p = 0.0047 α-syn treatment: F(1,18) = 1.966, p = 0.1778 Genotype: F(1,18) = 6.234, *p = 0.0225 |
| 2 A | GCase activity assay | Independent t test | Cortex: t(10) = 7.406, ****p < 0.0001 Striatum: t(10) = 3.023, *p = 0.0128 Hippocampus: t(10) = 6.870, ****p < 0.0001 Midbrain: t(10) = 4.593, ***p < 0.0010 |
| 2 C | Western blot: GCase (left), total synuclein (middle), p-α-syn (right) | Independent t test Mann–Whitney test Failed Shapiro–Wilk test |
GCase: t(4) = 1.093, p = 0.3360 Total synuclein: W = 4, p = 0.9999 |
| Independent t test | p-α-syn: t(9) = 2.808; *p = 0.0205 |
||
| 2 D | Western blot: vGlut1 (left), Homer1 (middle), Tuj1 (right) | Independent t test | vGlut1: t(5) = 6.686; **p = 0.0011 Homer1: t(4) = 1.481; p = 0.2127 Tuj1: t(9) = 0.05656, p = 0.9561 |
| 2 E | Western blot: SNAP25 (left), VAMP2 (middle), Syntaxin1a (right) | Independent t test | SNAP25: t(5) = 0005117, p = 0.9996 VAMP2: t(4) = 1.433, p = 0.2251 Syntaxin1a: t(6) = 0.3713, p = 0.7232 |
| 3 A | Open field test | Independent t test | Average velocity: t(10) = 2.002, p = 0.0732 Percent in center: t(11) = 1.436, p = 0.1790 Distance traveled: t(10) = 1.243, p = 0.2424 |
| 3 B | Pole test | Independent t test | Total descent time: t(10) = 2.638, *p = 0.0248 Turnaround time: t(12) = 0.2243, p = 0.8263 Time descending: t(11) = 1.467, p = 0.1704 |
| 3 C | Training | Repeated-measures two-way ANOVA | Time: F(4, 48) = 49.13, ****p < 0.0001 Genotype: F(1, 12) = 1.106, p = 0.3136 Time × genotype: F(4, 48) = 2.751, *p = 0.0386 |
| 3 C | Cued and contextual fear conditioning | Independent t test | Contextual: t(11) = 2.720, *p = 0.0199 Cued: t(12) = 2.069, p = 0.0608 |
| 4 A | GlcSph | Two-way ANOVA | Interaction: F(3,50) = 2.270, p = 0.0918 Age: F(3,50) = 23.54, p < 0.0001 Genotype: F(1,50) = 64.23, p < 0.0001 |
| 4 B | Total GlcCer | Two-way ANOVA | Interaction: F(3,50) = 1.454, p = 0.2384 Age: F(3,50) = 3.340, p = 0.0265 Genotype: F(1,50) = 2.493, p = 0.1206 |
| 4 C | GlcSph | Independent t test | t(9) = 2.810, *p = 0.0204 |
| 4 D | GlcCer | Independent t test | t(10) = 1.015, p = 0.3338 |
| 5 B | PFC | Two-way ANOVA | Interaction: F(1,16) = 6.890, p = 0.0184 Drug treatment: F(1,16) = 13.95, **p = 0.0018 Genotype: F(1,16) = 1.842, p = 0.1936 |
| 5 D | DG: granule cell layer CA1 pyramidal cell layer CA2-CA3 pyramidal cell layer |
Two-way ANOVA Independent t test |
Interaction: F(1,16) = 7.484, p = 0.0147 Drug treatment: F(1,16) = 0.05575, p = 0.8163 Genotype: F(1,16) =23.18, p = 0.0002 CA1 pyramidal cell layer: t(11) = 2.580; *p = 0.0256 CA2-CA3 pyramidal cell layer: t(13) = 1.997; p = 0.0672 |
| 5 F | SNc | Two-way ANOVA | Interaction: F(1,19) = 0.6662, p = 0.4245 Drug treatment: F(1,19) = 0.02359, p = 0.8795 Genotype: F(1,19) = 1.459, p = 0.2420 |
| 6 C | Estimated cell population | Three-way ANOVA | Interaction: F(1,34) = 0.06097, p = 0.8065 Drug treatment × α-syn treatment: F(1,34) = 0.2240, p = 0.6390 Drug treatment × genotype: F(1,34) = 0.06160, p = 0.8055 α-syn treatment × genotype: F(1,34) = 0.0002467, p = 0.9876 Drug treatment: F(1,34) = 4.451 *p = 0.0423 α-syn treatment: F(1,34) = 36.68 *p < 0.0001 Genotype: F(1,34) = 2.122, p = 0.1544 |
| 7 A | Survival curves | Kaplan–Meier survival curve | Post-monomer injection: Log-rank (Mantel–Cox) test: χ2 (3, N = 57) = 8.722, *p = 0.0332 Post-fibril injection: Log-rank (Mantel–Cox) test χ 2 (3, N = 42) = 0.6481, p = 0.8853 |
| 7 B | Open field test | Three-way ANOVA | Distance traveled: Interaction: F(1,66) = 1.655, p = 0.2028 Drug treatment × α-syn treatment: F(1,66) = 1.201, p = 0.2771 Drug treatment × genotype: F(1,66) = 0.01696, p = 0.8968 α-syn treatment × genotype: F(1,66) = 0.2655, p = 0.6081 Drug treatment: F(1,66) = 2.578, p = 0.1131 α-syn treatment: F(1,66) = 2.965, p = 0.0898 Genotype: F(1,66) = 1.084, p = 0.3016 Average velocity: Interaction: F(1,66) = 0.02006, p = 0.8878 Drug treatment × α-syn treatment: F(1,66) = 0.7082, p = 0.4031 Drug treatment × genotype: F(1,66) = 0.3206, p = 0.5732 α-syn treatment × genotype: F(1,66) = 0.6204, p = 0.4337 Drug treatment: F(1,66) = 5.121, p = 0.0269 α-syn treatment: F(1,66) = 0.5298, p = 0.4693 Genotype: F(1,66) = 0.05453, p = 0.8161 Percent in center: Interaction: F(1,70) = 0.5531, p = 0.4596 Drug treatment × α-syn treatment: F(1,70) = 0.0002562, p = 0.9873 Drug treatment × genotype: F(1,70) = 1.246, p = 0.2681 α-syn treatment × genotype: F(1,70) = 1.774, p = 0.1872 Drug treatment: F(1,70) = 5.160, *p = 0.0262 α-syn treatment: F(1,70) = 0.5955, p = 0.4429 Genotype: F(1,70) = 1.535, p = 0.2195 |
| 7 C | Pole test | Three-way ANOVA | Turnaround time: Interaction: F(1,69) = 2.500, p = 0.1184 Drug treatment × α-syn treatment: F(1,69) = 0.8307, p = 0.3652 Drug treatment × genotype: F(1,69) = 2.814, p =0.0980 α-syn treatment × genotype: F(1,69) = 0.4537, p = 0.5028 Drug treatment: F(1,69) = 6.223, *p = 0.0150 α-syn treatment: F(1,69) = 5.396, *p = 0.0231 Genotype: F(1,69) = 0.1263, p = 0.7234 Time descending: Interaction: F(1,62) = 0.2636, p = 0.6095 Drug treatment × α-syn treatment: F(1,62) = 0.4947, p = 0.4845 Drug treatment × genotype: F(1,62) = 0.3006, p = 0.5855 α-syn treatment × genotype: F(1,62) = 0.3767, p = 0.5416 Drug treatment: F(1,62) = 0.2163, p = 0.6435 α-syn treatment: F(1,62) = 4.483, *p = 0.0382 Genotype: F(1,62) = 4.874, *p = 0.0310 Total descent time: Interaction: F(1,62) = 0.003431, p = 0.9535 Drug treatment × α-syn treatment: F(1,62) = 0.8643, p = 0.3561 Drug treatment × genotype: F(1,62) = 0.09758, p = 0.7558 α-syn treatment × genotype: F(1,62) = 0.7574, p = 0.3875 Drug treatment: F(1,62) = 3.983, p = 0.0504 α-syn treatment: F(1,62) = 4.805, p = 0.0321 Genotype: F(1,62) = 2.267, p = 0.1372 |
| 7 D | Training | Repeated-measures three-way ANOVA | Training: control Interaction: F(4240) = 0.6830, p = 0.6044 Time × α-syn treatment: F(4240) = 4.425, **p = 0.0018 Time × genotype: F(4240) = 0.0877, p = 0.9862 α-syn treatment × genotype: F(1,60) = 0.6170, p = 0.4353 Time: F(4240) = 120.1, ****p < 0.0001 α-syn treatment: F(1,60) = 2.12, p = 0.1506 Genotype: F(1,60) = 0.4373, p = 0.5110 Training: venglustat Interaction: F(4,64) = 0.5828, p = 0.6762 Time × α-syn treatment: F(4,64) = 0.5808, p = 0.6776 Time × genotype: F(4,64) = 0.8026, p = 0.5280 α-syn treatment × genotype: F(1,16) = 0.1628, p = 0.6919 Time: F(2.882,46.11) = 25.40, ****p < 0.0001 α-syn treatment: F(1,16) = 0.006116, p = 0.9386 Genotype: F(1,16) = 1.846, p = 0.1931 |
| 7 E | Cued and contextual fear conditioning | Three-way ANOVA | Cued: Interaction: F(1,76) = 0.03063, p = 0.8615 Drug treatment × α-syn treatment: F(1,76) = 1.378, p = 0.2441 Drug treatment × genotype: F(1,76) = 1.865, p = 0.1761 α-syn treatment × genotype: F(1,76) = 0.6219, p = 0.4328 Drug treatment: F(1,76) = 1.757, p = 0.1890 α-syn treatment: F(1,76) = 5.703, *p = 0.0194 Genotype: F(1,76) = 1.960, p = 0.1656 Contextual: Interaction: F(1,76) = 0.07405, p = 0.7863 Drug treatment × α-syn treatment: F(1,76) = 0.07986, p = 0.7783 Drug treatment × genotype: F(1,76) = 0.3424, p = 0.5602 α-syn treatment × genotype: F(1,76) = 0.2234, p = 0.6378 Drug treatment: F(1,76) = 0.0002150, p = 0.9883 α-syn treatment: F(1,76) = 1.850, p = 0.1778 Genotype: F(1,76) = 3.979, *p = 0.0497 |
| Extended Data Figure 1-1B | Percent area of NF (left) and p-α-syn (right) | Two-way ANOVA | Neurofilament: Interaction: F(1,16) = 0.4965, p = 0.4912 Drug treatment: F(1,16) = 0.2427, p = 0.6290 Genotype: F(1,16) = 0.01635, p = 0.8999 p-α-syn: Interaction: F(1,16) = 0.007994, p = 0.9299 Drug treatment: F(1,16) = 0.09064, p = 0.7672 Genotype: F(1,16) = 0.5849, p = 0.4555 |
| Extended Data Figure 1-2A | GlcCer | Three-way ANOVA | Interaction: F(3151) = 1.524, p = 0.2106 Dose × α-syn treatment: F(3151) = 0.3454, p = 0.7926 Dose × genotype: F(3151) = 0.7284, p = 0.5365 Genotype × α-syn treatment: F(1151) = 3.856, p = 0.0514 Dose: F(3151) = 28.06, ****p < 0.0001 α-syn treatment: F(1151) = 1.454, p = 0.2299 Genotype: F(1151) = 0.1898, p = 0.6637 |
| Extended Data Figure 1-2B | Sphingomyelin | Three-way ANOVA | Interaction: F(3151) = 0.2265, p = 0.8778 Dose × α-syn treatment: F(3151) = 0.3922, p = 0.7588 Dose × genotype: F(3151) = 0.3684, p = 0.7759 Genotype × α-syn treatment: F(1151) = 0.7365, p = 0.3921 Dose: F(3151) = 11.11, ****p < 0.0001 α-syn treatment: F(1151) = 0.6928, p = 0.4065 Genotype: F(1151) = 0.08458, p = 0.7716 |
| Extended Data Figure 1-2C | Sphingosine | Three-way ANOVA | Interaction: F(3157) = 1.152, p = 0.3302 Dose × α-syn treatment: F(3157) = 0.4860, p = 0.6925 Dose × genotype: F(3157) = 1.166, p = 0.3245 Genotype × α-syn treatment: F(1157) = 1.259, p = 0.2636 Dose: F(3157) = 1.922, p = 0.1283 α-syn treatment: F(1157) = 0.05604, p = 0.8132 Genotype: F(1157) = 0.5954, p = 0.4415 |
| Extended Data Figure 1-2D | Ceramide | Three-way ANOVA | Interaction: F(3151) = 1.515, p = 0.2128 Dose × α-syn treatment: F(3151) = 0.2502, p = 0.8611 Dose × genotype: F(3151) = 0.2116, p = 0.8882 Genotype × α-syn treatment: F(1151) = 5.610, *p = 0.0191 Dose: F(3151) = 4.115, **p = 0.0077 α-syn treatment: F(1151) = 0.01056, p = 0.9183 Genotype: F(1151) = 0.08041, p = 0.7771 |
| Extended Data Figure 1-3B | Internalization of PFF-488 | Two-way ANOVA | Interaction: F(1,6) = 0.3480, p = 0.5768 Drug treatment: F(1,6) = 0.07183, p = 0.7977 Genotype: F(1,6) = 0.03039, p = 0.8673 |
| Extended Data Figure 1-4B | Total α-synuclein at DIV7 (left) and DIV21 (right) | Independent t test | DIV7: t(3) = 0.3553, p = 0.7459 DIV21: t(5) = 0.04483, p = 0.9660 |
| Extended Data Figure 1-4D | Total α-synuclein | Two-way ANOVA | Interaction: F(1,2) = 0.005705, p = 0.9467 Drug treatment: F(1,2) = 0.3405, p = 0.6186 Genotype: F(1,2) = 3.430, p = 0.2052 |
| Extended Data Figure 1-5B | CatB activity | Nested two-way ANOVA | Interaction: F(1,51) = 2.758, p = 0.1029 Drug treatment: F(1,51) = 10.27, **p = 0.0023 Genotype: F(1,51) = 7.014, *p = 0.0107 |
| Extended Data Figure 4-1A | GlcCer C18:0 | Two-way ANOVA | Interaction: F(3,50) = 2.173, p = 0.1028 Age: F(3,50) = 12.77, p < 0.0001 Genotype: F(1,50) = 0.2353, p = 0.6297 |
| Extended Data Figure 4-1B | GlcCer C20:0 | Two-way ANOVA | Interaction: F(3,48) = 0.6806, p = 0.5682 Age: F(3,48) = 0.7990, p = 0.5005 Genotype: F(1,48) = 1.619, p = 0.2094 |
| Extended Data Figure 4-1C | GlcCer C22:0 | Two-way ANOVA | Interaction: F(3,50) = 0.3007, p = 0.8247 Age: F(3,50) = 1.027, p = 0.3886 Genotype: F(1,50) = 2.898, p = 0.0949 |
| Extended Data Figure 4-1D | GlcCer C24:1 | Two-way ANOVA | Interaction: F(3,50) = 0.7606, p = 0.5215 Age: F(3,50) = 1.821, p = 0.1554 Genotype: F(1,50) = 9.377, **p = 0.0035 |
| Extended Data Figure 5-1A | Aggregate burden of the amygdala | Mann–Whitney Test Failed Shapiro–Wilk test |
W = 11, p = 0.1690 |
| Extended Data Figure 5-1B | Aggregate burden of the entorhinal cortex | Independent t test | t(11) = 0.03628; p = 0.9717 |
| Extended Data Figure 5-1C | Ceramide | Three-way ANOVA | Interaction: F(1,35) = 0.9955, p = 0.3253 Drug treatment × α-syn treatment: F(1,35) = 2.536, p = 0.1203 Drug treatment × genotype: F(1,35) = 5.255, *p = 0.0280 α-syn treatment × genotype: F(1,35) = 0.6352, p = 0.4308 Drug treatment: F(1,35) = 7.185, *p = 0.0111 α-syn treatment: F(1,35) = 1.582, p = 0.2168 Genotype: F(1,35) = 7.241, *p = 0.0109 |
| Extended Data Figure 5-2D | Sphingomyelin | Three-way ANOVA | Interaction: F(1,35) = 7.734, **p = 0.0087 Drug treatment × α-syn treatment: F(1,35) = 3.327, p = 0.0767 Drug treatment × genotype: F(1,35) = 3.289, p = 0.0783 α-syn treatment × genotype: F(1,35) = 8.184, **p = 0.0071 Drug treatment: F(1,35) = 24.29, ****p < 0.0001 α-syn treatment: F(1,35) = 0.7393, p = 0.3957 Genotype: F(1,35) = 2.626, p = 1141 |
| Extended Data Figure 5-2E | Sphingosine-1-phosphate | Three-way ANOVA | Interaction: F(1,32) = 0.008874, p = 0.9255 Drug treatment × α-syn treatment: F(1,32) = 3.188, p = 0.0836 Drug treatment × genotype: F(1,32) = 0.04317, p = 0.8367 α-syn treatment × genotype: F(1,32) = 0.6178, p = 0.4376 Drug treatment: F(1,32) = 1.016, p = 0.3209 α-syn treatment: F(1,32) = 9.109, **p = 0.0050 Genotype: F(1,32) = 0.1771, p = 0.6767 |
| Extended Data Figure 5-3 | NeuN count: dmPFC | Two-way ANOVA | Interaction: F(1,16) = 0.07678, p = 0.7853 Drug treatment: F(1,16) = 0.02827, p = 0.8686 Genotype: F(1,16) = 2.821, p = 0.1124 |
| Extended Data Figure 5-5 | Total α-syn expression | Two-way ANOVA | Interaction: F(3,16) = 0.01274, p = 0.9979 Brain region: F(3,16) = 0.4320, p = 0.7329 Genotype: F(1,16) = 0.007856, p = 0.9305 |