Introduction
Materials and methods
Sample collection
Sample classification
Discovery cohort | Validation cohort | |||
---|---|---|---|---|
A-T- with SCD | A+T+ | A-T- with SCD | A+T+ | |
Number of individuals | 106 | 65 | 26 | 26 |
Diagnosis - SCD/MCI/AD | 106/0/0 | 11/19/35 | 26/0/0 | 0/0/26 |
Agea,b | 59 (51 –69) | 62 (51–74) | 59 (51–68) | 60 (51–68) |
Sex - F/Mc | 65/41 | 41/24 | 6/20 | 17/9 |
Aβ42 (pg/ml)a | 1160 (562–2000) | 540 (248–990) | 1106 (867–1495) | 636 (274–804) |
Aβ40 (pg/ml) ÷ 10 a | 1134 (542–1923) | 1225 (558–2185) | - | - |
Aβ42/Aβ40 × 10a | 1.01 (0.73–1.29) | 0.47 (0.26–0.67) | - | - |
t-tau (pg/ml)a | 214 (75–907) | 538 (324–1210) | 232 (88–349) | 784 (413–2160) |
p-tau (pg/ml)a | 32 (14–56) | 82 (57–190) | 38 (22–50) | 94 (64–185) |
NfL (pg/ml) a,d | 670 (310–3960) | 1,130 (650–6,550) | - | - |
Albumin CSF/serum ratioe | 5.70 (2.50–14.40) | 5.4 (2.6–11.1) | - | - |
MMSE a,f | 28.0 (16.0–30.0) | 23.0 (14.0–30.0) | 29 (25–30) | 22 (6–28) |
MoCA a,f | 26.0 (13–30.0) | 20.0 (5.0–28.0) | - | - |
KOD a,f | 56 (23–98) | 44 (1–72) | - | - |
RAVLT a,f | 50 (27–69) | 31 (3–64) | - | - |
RCF a,f | 18 (2–32) | 9 (0–33) | - | - |
Protein analysis with suspension bead array
CSF amyloid, tau, NfL and CSF and serum albumin measurements
Data analysis and visualizations
Data adjustment and quality control
Univariate analysis
Protein clustering
Support vector machine modelling
Cognitive data correlation analysis
Results
Brain-derived proteins associate differently with CSF amyloid and tau
Protein pairs from different clusters predict amyloid and tau status with high accuracy
Tau-associated protein | Amyloid-associated protein | AUC (CI) discovery | AUC (CI) validation |
---|---|---|---|
GAP43 | PTPRN2 | 0.98 (0.93–1) | 0.98 (0.94–1) |
GAP43 | NCAN | 0.96 (0.9–1) | 0.94 (0.86–1) |
GAP43 | TMEM132D | 0.96 (0.89–1) | 0.99 (0.98–1) |
GAP43 | CHL1 | 0.95 (0.88–1) | 0.97 (0.92–1) |
GAP43 | CCK | 0.95 (0.87–1) | 0.94 (0.87–0.99) |
GAP43 | NPTX2 | 0.94 (0.84–1) | 0.97 (0.91–1) |
GAP43 | CDH8 | 0.94 (0.84–1) | 0.98 (0.92–1) |
NRGN | PTPRN2 | 0.94 (0.83–1) | 0.94 (0.87–0.99) |
SNCB | PTPRN2 | 0.93 (0.84–1) | 1 (0.98–1) |
GAP43 | PAM | 0.93 (0.84–0.99) | 0.98 (0.95–1) |
SNCB | CCK | 0.93 (0.84–0.99) | 0.95 (0.89–1) |
GAP43 | OMG | 0.93 (0.84–0.99) | 0.91 (0.83–0.98) |
GAP43 | APLP1 | 0.93 (0.84–0.99) | 0.89 (0.79–0.96) |
GAP43 | NPTXR | 0.93 (0.84–1) | 0.87 (0.75–0.97) |
AMPH | PTPRN2 | 0.92 (0.81–0.99) | 0.93 (0.86–0.98) |
GAP43 | NRCAM | 0.92 (0.8–0.99) | 0.9 (0.81–0.97) |
NRGN | NCAN | 0.92 (0.83–0.99) | 0.9 (0.8–0.98) |
GAP43 | NPTX1 | 0.91 (0.8–0.99) | 0.9 (0.8–0.97) |
GAP43 | KIAA1549L | 0.91 (0.8–1) | 0.88 (0.76–0.97) |