Table 3.
CSF biomarker levels by Aβ group
| Definition 1 (n = 318) |
Definition 2 (n = 313*) |
Definition 3 (n = 318) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aβ- | Low burden | Aβ+ | Aβ- | Low burden | Aβ+ | Aβ- | Low burden | Aβ+ | ||||
| CSF- CL < 30 (n = 205, 64.5%) |
CSF+ CL < 30 (n = 88, 27.7%) |
CSF+ CL > 30 (n = 25, 7.86%) |
P value | CSF- VR- (n = 202, 64.5%) |
CSF+ VR- (n = 72, 23.0%) |
CSF+ VR+ (n = 39, 12.5%) |
P value | CL < 20 (n = 281, 88.4%) |
20–40 CL (n = 18, 5.66%) |
CL > 40 (n = 19, 6.0%) |
P value | |
| p-tau (pg/ml) | 13.9 (4.19) | 16.5 (5.97)1 | 25.9 (6.94)1 | <0.0001 | 13.8 (4.17) | 16.2 (6.03)2 | 23.1 (7.40)1 | <0.0001 | 14.6 (4.97) | 19.6 (7.13)2 | 25.3 (7.08)1 | <0.0001 |
| t-tau (pg/ml) | 176 (48.7) | 202 (64.9)3 | 293 (71.6)1 | <0.0001 | 176 (48.5) | 199 (66.1)2 | 267 (75.1)1 | <0.0001 | 183 (55.9) | 239 (85.4)2 | 280 (65.8)1 | <0.0001 |
| NfL (pg/ml) | 75.3 (23.6) | 83.6 (23.4)4 | 114 (31.1)1 | <0.0001 | 75.4 (23.7) | 82.3 (22.9) | 105 (31.4)1 | <0.0001 | 77.4 (23.6) | 98.5 (31.2) | 112 (33.4)3 | 0.0004 |
| Neurogranin (pg/ml) | 722 (252) | 802 (325)4 | 1103 (311)1 | <0.0001 | 719 (251) | 794 (330) | 1019 (324)1 | <0.0001 | 747 (282) | 951 (402)4 | 1003 (239)2 | 0.0009 |
| sTREM2 (ng/ml) | 7.58 (1.93) | 7.75 (2.15) | 9.39 (2.83)2 | 0.006 | 7.57 (1.93) | 7.74 (2.22) | 8.83 (2.63) | 0.053 | 7.63 (2.00) | 8.84 (2.74) | 8.79 (2.66) | 0.065 |
| YKL40 (ng/ml) | 138 (44.8) | 145 (49.8) | 206 (58.5)1 | 0.0002 | 137 (44.6) | 143 (51.4) | 187 (58.5)3 | 0.002 | 140 (46.6) | 170 (55.1) | 200 (64.1)2 | 0.004 |
| GFAP (ng/ml) | 7.09 (2.13) | 7.68 (2.32) | 9.68 (2.58)3 | 0.001 | 7.08 (2.14) | 7.67 (2.39) | 9.00 (2.58)2 | 0.011 | 7.24 (2.22) | 8.51 (1.91) | 9.71 (2.74)2 | 0.004 |
| IL6 (pg/ml) | 3.86 (1.33) | 3.81 (1.54) | 3.97 (1.37) | 0.33 | 3.87 (1.33) | 3.90 (1.58) | 3.72 (1.39) | 0.89 | 3.86 (1.38) | 3.66 (1.58) | 3.94 (1.37) | 0.56 |
| S100B (ng/ml) | 0.98 (0.20) | 1.06 (0.26) | 1.07 (0.25) | 0.054 | 0.98 (0.20) | 1.05 (0.25) | 1.09 (0.27) | 0.044 | 1.00 (0.21) | 1.16 (0.33) | 1.03 (0.18) | 0.093 |
| α-synuclein (pg/ml) | 189 (80.9) | 190 (62.5) | 249 (87.3)2 | 0.005 | 189 (81.2) | 184 (60.9) | 239 (79.2)3 | 0.001 | 190 (76.6) | 210 (82.3) | 237 (85.1) | 0.069 |
Data are expressed as mean (M) and standard deviation (SD). One-way ANCOVA adjusted by age and sex, followed by Dunnett-corrected post hoc comparisons, was used to compare CSF biomarker values between groups. The P values indicated in the last column refer to the group main effect. Significant P values are marked in bold. All P values remained significant after FDR multiple comparison correction, except S100B in definition 2 (P = 0.055). “Low burden” refers to “low burden of Aβ pathology”. Abbreviations: Aβ amyloid-β, CL Centiloid, CSF cerebrospinal fluid, p-tau phosphorylated tau, t-tau total tau, NfL neurofilament light, S100B S100 calcium-binding protein B, sTREM2 soluble triggering receptor expressed on myeloid cells 2 (TREM2), GFAP glial fibrillary acidic protein, IL6 interleukin 6, VR visual read, YKL40 Chitinase-3-like protein 1
*In definition 2, we included 313 participants because 2 participants did not have Aβ PET visual read assessment available and 3 additional participants had a discrepant CSF and visual read assessment (negative CSF Aβ42/40 ratio but positive visual read). Participants with this biomarker profile do not fall in any of the definition 2 categories
1P < 0.0001 vs Aβ- group
2P < 0.01 vs Aβ- group
3P < 0.001 vs Aβ- group
4P < 0.05 vs Aβ- group