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. 2024 May 15;20(6):4159–4173. doi: 10.1002/alz.13835

TABLE 3.

Unadjusted and adjusted linear models assessing associations between plasma and neuroimaging biomarkers.

Aβ‐PET Base (N = 140) Adj (N = 81) F‐Adj (N = 77) F‐Adj‐Dx (N = 77)
Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q
NfL 0.46 4.9 0.27, 0.65 <0.001 <0.001 0.34 2.6 0.08, 0.61 0.011 0.033 0.04 0.2 −0.30, 0.38 0.800 0.800 0.01 −0.1 −0.30, 0.28 >0.9 >0.9
GFAP 0.53 9.1 0.42, 0.65 <0.001 <0.001 0.49 5.7 0.32, 0.67 <0.001 <0.001 0.35 3.8 0.17, 0.54 0.002 0.014 0.35 4.3 0.18, 0.51 0.002 0.023
Aβ42/40 −0.46 −3.7 −0.61, −0.18 <0.001 <0.001 −0.23 −1.8 −0.49, 0.02 0.039 0.059 −0.06 −0.7 −0.24, 0.11 0.600 0.800 −0.05 −0.6 −0.21, 0.12 0.700 0.800
p‐tau181 0.55 5.6 0.36, 0.76 <0.001 <0.001 0.63 8.0 0.48, 0.79 <0.001 <0.001 0.56 8.2 0.42, 0.70 <0.001 <0.001 0.54 8.4 0.41, 0.67 <0.001 <0.001
PLASMA SUM 0.63 11.5 0.52, 0.74 <0.001 <0.001 0.66 8.22 0.50, 0.82 <0.001 <0.001 0.51 4.52 0.29, 0.74 <0.001 0.002 0.48 4.34 0.26, 0.70 <0.001 0.004
BVOL Base (N = 524) Adj (N = 383) F‐Adj (N = 374) F‐Adj‐Dx (N = 374)
Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q
NfL −0.5 −12.1 −0.53, −0.38 <0.001 <0.001 −0.46 −8.9 −0.56, −0.36 <0.001 <0.001 −0.16 −3.7 −0.24, −0.07 0.002 0.005 −0.14 −3.3 −0.23, −0.06 0.005 0.017
GFAP −0.4 −9.4 −0.42, −0.27 <0.001 <0.001 −0.33 −6.7 −0.41, −0.22 <0.001 <0.001 −0.13 −3.5 −0.20, −0.06 0.005 0.013 −0.12 −3.2 −0.20, −0.05 0.009 0.028
Aβ42/40 0.2 4.5 0.10, 0.27 <0.001 <0.001 0.13 2.8 0.04, 0.21 0.013 0.019 0.01 0.2 −0.06, 0.07 0.800 0.800 0.00 0.1 −0.06, 0.07 >0.9 >0.9
p−tau181 −0.4 −7.7 −0.45, −0.27 <0.001 <0.001 −0.30 −5.9 −0.41, −0.20 <0.001 <0.001 −0.13 −2.8 −0.22, −0.04 0.006 0.015 −0.12 −2.5 −0.21, −0.03 0.010 0.033
PLASMA SUM −0.5 −13 −0.54, −0.40 <0.001 <0.001 −0.45 −8.84 −0.55, −0.35 <0.001 <0.001 −0.17 −3.85 −0.26, −0.08 <0.001 0.002 −0.16 −3.4 −0.25, −0.07 0.002 0.006
WMH Base (N = 524) Adj (N = 383) F‐Adj (N = 374) F‐Adj‐Dx (N = 374)
Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q
NfL 0.4 10.2 0.32, 0.48 <0.001 <0.001 0.37 7.2 0.27, 0.47 <0.001 <0.001 0.13 2.4 0.02, 0.23 0.024 0.100 0.09 1.7 −0.01, 0.19 0.120 0.300
GFAP 0.4 10.4 0.30, 0.44 <0.001 <0.001 0.31 6.6 0.21, 0.40 <0.001 <0.001 0.16 3.4 0.07, 0.25 0.002 0.007 0.14 3.0 0.05, 0.23 0.007 0.031
Aβ42/40 −0.1 −3.2 −0.23, −0.05 0.600 0.600 −0.10 −2.0 −0.19, 0.00 0.042 0.063 0.02 −0.4 −0.10, 0.06 0.700 0.800 0.00 −0.1 −0.08, 0.08 >0.9 >0.9
p‐tau181 0.3 6.2 0.18, 0.36 <0.001 <0.001 0.20 4.0 0.10, 0.30 <0.001 <0.001 0.13 2.5 0.03, 0.22 0.013 0.053 0.10 2.0 0.00, 0.20 0.048 0.200
PLASMA SUM 0.41 11.3 0.34, 0.48 <0.001 <0.001 0.36 7.79 0.27, 0.45 <0.001 <0.001 0.18 3.37 0.07, 0.28 0.002 0.006 0.14 2.62 0.04, 0.25 0.013 0.041
FA Base (N = 469) Adj (N = 346) F‐Adj (N = 339) F‐Adj‐Dx (N = 339)
Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q
NfL −0.2 −4.0 −0.29, −0.10 <0.001 <0.001 −0.23 −4.5 −0.33, −0.13 <0.001 <0.001 −0.10 −1.6 −0.22, 0.03 0.200 0.400 −0.11 −1.8 −0.24, 0.01 0.100 0.300
GFAP −0.2 −5.1 −0.30, −0.13 <0.001 <0.001 −0.24 −4.7 −0.34, −0.14 <0.001 <0.001 −0.16 −2.9 −0.27, −0.05 0.009 0.035 −0.16 −2.9 −0.27, −0.05 0.007 0.031
Aβ42/40 0.0 0.5 −0.07, 0.11 0.600 0.600 0.00 −0.1 −0.09, 0.09 >0.9 >0.9 0.03 −0.8 −0.12, 0.05 0.500 0.700 0.03 −0.7 −0.12, 0.05 0.600 0.800
p‐tau181 −0.2 −3.1 −0.25, −0.05 0.001 0.001 −0.11 −2.1 −0.21, −0.01 0.055 0.082 −0.10 −1.7 −0.21, 0.01 0.100 0.200 −0.12 −2.0 −0.23, 0.00 0.062 0.200
PLASMA SUM −0.2 −4.72 −0.29, −0.12 <0.001 <0.001 −0.21 −4.07 −0.31, −0.11 <0.001 <0.001 −0.13 −2.07 −0.25, −0.01 0.063 0.200 −0.15 −2.33 −0.27, −0.02 0.034 0.089
FW Base (N = 443) Adj (N = 323) F‐Adj (N = 318) F‐Adj‐Dx (N = 318)
Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q Beta Z 95% CI 1 p q
NfL 0.3 5.0 0.19, 0.43 <0.001 <0.001 0.33 4.5 0.18, 0.47 <0.001 <0.001 0.12 1.5 −0.03, 0.27 0.100 0.200 0.10 1.3 −0.05, 0.25 0.200 0.300
GFAP 0.3 5.0 0.15, 0.35 <0.001 <0.001 0.24 3.8 0.12, 0.37 <0.001 <0.001 0.17 2.5 0.04, 0.30 0.008 0.020 0.16 2.5 0.03, 0.29 0.011 0.028
Aβ42/40 −0.1 −1.6 −0.15, 0.02 0.200 0.200 −0.05 −1.0 −0.14, 0.05 0.400 0.400 0.01 0.3 −0.07, 0.09 0.800 0.800 0.02 0.5 −0.06, 0.10 0.700 0.700
p‐tau181 0.2 3.9 0.10, 0.30 <0.001 <0.001 0.15 2.6 0.04, 0.26 0.013 0.022 0.02 0.4 −0.10, 0.15 0.700 0.800 0.01 0.2 −0.12, 0.14 0.900 >0.9
PLASMA SUM 0.29 5.74 0.19, 0.39 <0.001 <0.001 0.28 4.46 0.16, 0.40 <0.001 <0.001 0.12 1.67 −0.02, 0.26 0.100 0.200 0.10 1.38 −0.04, 0.24 0.200 0.300

Note: Base (unadjusted) and adjusted models associating plasma and neuroimaging‐derived biomarkers are presented. Modest associations were observed between plasma and neuroimaging markers prior to and after adjustment with eGFR and BMI. In fully adjusted models, GFAP remained associated with all imaging biomarkers except gmCBF. Plasma biomarkers and gmCBF were weakly associated in unadjusted models only. p‐tau181, GFAP, and the plasma composite (Plasma Sum) were most strongly associated with Aβ‐PET, and NfL with BVOL before and after adjustment.

Abbreviations: Adj, linear models adjusted for comorbidities (eGFR, BMI) and covariates (age, sex, race, education, APOE ε4 status, and antihypertensive medication);Aβ, amyloid beta; Base: baseline unadjusted models; BVOL, brain volume (adjusted for intracranial volume); CU, cognitively unimpaired; DEM, dementia; DWI, diffusion weighted imaging; Dx, diagnosis; FA, fraction anisotropy; F‐Adj‐Dx, fully adjusted linear models adding in diagnostic status (Dx: CU, MCI, DEM); FW, free water; GFAP, glial fibrillary acidic protein; MCI, mild cognitive impairment; NfL, neurofilament light chain; NODDI, neurite orientation dispersion and density imaging; q, Benjamini–Hochberg false discovery rate; SUVr, standardized uptake value ratio; WMH, log‐transformed global white matter hyperintensity values.

Bold values represent plasma biomarker coefficient significant at p < 0.05.