Table 3A.
Overview inflammatory biomarkers associated with longitudinal clinical measures in AD publications.
| Biomarker | Study | Quality | Cohort (n) | Age (y) | MMSE | Associated clinical outcome measure (follow-up time): statistical analysis | Result statistical analysis |
|---|---|---|---|---|---|---|---|
| MCP-1 (CCL2) | Pillai, 2020 | L | MCI-AD (48) | 68.1 | 24.8 | δMMSE (9m)* | β = -1.540 |
| δMMSE (15m)* | β = -2.360 | ||||||
| δCDR-SB (9m)* | β = 1.230 | ||||||
| δCDR-SB (15m) (MCI-AD: n = 40) |
R = 0.540 | ||||||
| δCDR-SB (15m)* | β = 2.820 | ||||||
| MCI (134) | 74.9 | 26.9 | δMMSE (12m)* | β = -1.450 | |||
| δMMSE (24m)* | β = -1.460 | ||||||
| δMMSE (36m)* | β = -2.870 | ||||||
| δCDR-SB (24m)* | β = 0.860 | ||||||
| δCDR-SB (36m)* | β = 1.430 | ||||||
| δCDR-SB (36m) | R = 0.240 | ||||||
| δCDR-SB (36m) (MCI-AD: n = 97) |
R = 0.270 | ||||||
| Westin, 2012 | L | MCI-AD (47) | 74.0 | 26.7 | Annual decline MMSE (60m) | R = 0.420 | |
| Annual decline MMSE (60m)° | β = 0.390 | ||||||
| CCL4 | Pillai, 2020 | L | MCI (134) | 74.9 | 26.9 | δMMSE (36m)* | β = -1.360 |
| δCDR-SB (36m)* | β = 0.760 | ||||||
| CCL5 | Pillai, 2020 | L | MCI (134) | 74.9 | 26.9 | δMMSE (24m)* | β = -0.430 |
| δCDR-SB (24m) (MCI: n = 118) |
R = 0.190 | ||||||
| δCDR-SB (24m)* | β = 0.410 | ||||||
| YKL-40 (CHI3L1) | Kester, 2015 | M | MCI (61) | 68.0 | 27.0 | MMSE decline: predictor (32m) | β = -0.320 |
| AD (65) | 65.0 | 22.0 | MMSE decline: predictor (46m) | β = 0.650 | |||
| Complement factor C3 | Toledo, 2014 | M | MCI (163) | 74.5 | 27.0 | ADAS-Cog: C3xTime (42m) | β = -0.120 |
| AD (83) | 74.8 | 23.7 | ADAS-Cog: C3xTime (22m) | β = -0.009 | |||
| Factor H (FH) | Toledo 2014 | M | MCI (163) | 74.5 | 27.0 | ADAS-Cog: FHxTime (42m) | β = -0.075 |
| AD (83) | 74.8 | 23.7 | ADAS-Cog: FHxTime (22m) | β = -0.005 | |||
| FGF basic | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.664 |
| Fibrinogen (FGA) | Pillai, 2020 | L | MCI-AD (48) | 68.1 | 24.8 | δCDR-SB (15m)* | β = -0.270 |
| MCI (134) | 74.9 | 26.9 | δMMSE (12m)* | β = 0.490 | |||
| δCDR-SB (24m) | R = -0.180 | ||||||
| δCDR-SB (24m)* | β = -0.230 | ||||||
| Gas-6 | Sainaghi, 2017 | M | AD (50) | 65.0 | 22.0 | MMSE decline (24m) | R = -0.800 |
| G-CSF | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.521 |
| GM-CSF | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.479 |
| Tarkowski, 2003 | L | MCI (56) | 72.0 | 28.9 | MMSE (9m) (n = 0) |
R = NR | |
| IFN-γ | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.495 |
| IL-1β | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.576 |
| Tarkowski, 2003 | L | MCI (56) | 72.0 | 28.9 | MMSE (9m) (n = 6) |
R = 0.340 | |
| δMMSE (9m) (n = 6) |
R = 0.300 | ||||||
| IL-4 | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.507 |
| IL-6 | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.553 |
| IL-9 | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.578 |
| IL-17 | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.577 |
| MIP-1β | Taipa, 2019 | M | AD (32) | 62.7 | 18.2 | δDRS-2 (12m) | R = -0.577 |
| MMP3 | Pillai, 2020 | L | MCI-AD (48) | 68.1 | 24.8 | δMMSE (9m) (MCI-AD: n = 40) |
R = 0.380 |
| δMMSE (9m)* | β = 2.050 | ||||||
| δCDR-SB (9m) (MCI-AD: n = 39) |
R = -0.36 | ||||||
| δCDR-SB (9m)* | β = -0.970 | ||||||
| δCDR-SB (15m)* | β = -0.940 | ||||||
| MCI (134) | 74.9 | 26.9 | δCDR-SB (36m)* | β = -0.530 | |||
| sTNFR1 score | Hu, 2021 | H | MCI (174) | 75.2 | NR | δCDR-SB (60m) | β = -0.026 |
| δCDR-SB (60m): sTNFR1 score x Months | β = -0.020 | ||||||
| Time to CDR > 4.0: High AD + High sTNFR1 scores | Longer than Low sTNFR1 | ||||||
| Risk for CDR > 4.0: High AD + High sTNFR1 scores | HR = 0.454 | ||||||
| δADNI-Mem-EF (60m) | β = -0.010 | ||||||
| δADNI-Mem-EF (60m): sTNFR1 score x Months | β = 0.005 | ||||||
| sTREM2 | Pillai, 2021 | L | MCI (67) | 74.1 | 26.8 | CDR-SB decline (60m): sTREM2 x Visit number | β = 0.016 |
| AD (42) | 74.2 | 23.5 | CDR-SB decline (60m): sTREM2 x Visit number | β = -1.334 | |||
| sTREM2 score | Hu, 2021 | H | AD (97) | 75.1 | NR | δCDR-SB (36m) | β = 0.004 |
| δCDR-SB (36m): sTREM2 score x Months | β = -0.040 | ||||||
| Time to CDR-SB > 7.8 (36m): High AD + High sTREM2 score | Longer than Low sTREM2 | ||||||
| Time to CDR-SB > 7.8 (36m): High p-Tau + High sTREM2 score | Longer than Low sTREM2 | ||||||
| Risk to CDR-SB > 7.8 (36m): High AD + High sTREM2 scores | HR = 0.412 | ||||||
| δADNI-Mem-EF (36m) | β = -0.027 | ||||||
| δADNI-Mem-EF (36m): sTREM2 score x Months | β = 0.006 |
β, regression coefficient; AD, Alzheimer’s disease; ADAS-Cog, Alzheimer’s Disease Assessment Scale – Cognitive Subscale; ADNI-Mem-EF, Average of composite Alzheimer’s Disease Neuroimaging Initiative Memory and Executive Functioning Scores; CDR-SB, Clinical Dementia Rating – Sum of Boxes; DRS-2, Dementia Rating Scale-2; H, High quality; HR, Hazard ratio; L, Low quality; m, months; M, Moderate quality; MCI, Mild Cognitive Impairment; MCI-AD, MCI with AD biomarkers and/or AD diagnosis at follow-up; MMSE, Mini-Mental State Examination; n, number; R, Spearman or Pearson correlation coefficient. Significant p-values are marked in bold. *Multivariable analyses; °Multivariate analyses.