The longitudinal trajectory of CSF sTREM2: the alzheimer’s disease neuroimaging initiative

Table 2 Longitudinal trajectory of CSF sTREM2 and the association of CSF sTREM2 with sex using longitudinal data, ADNI cohort, United States and Canada, 2004–2021

Variables	Model 1^a	Model 2^b	Model 3^c	Model 4^d	Model 5^e	Model 6^f
Age (years)	0.023 (0.002) ^***g	0.023 (0.002) ^***	0.022 (0.002) ^***	0.022 (0.002) ^***	0.018 (0.002) ^***	0.020 (0.002) ^***
Sex (referent: men)		0.013 (0.031)	0.025 (0.031)	0.043 (0.034)	-0.037 (0.029)	0.016 (0.031)
Race/ethnicity (referent: Non-Hispanic white)			-0.336 (0.053) ^***	-0.329 (0.053) ^***	-0.220 (0.046) ^***	-0.304 (0.053) ^***
TREM2 rare variant carrying status			-0.107 (0.095)	-0.112 (0.096)	-0.130 (0.081)	-0.150 (0.094)
APOE ε4 allele status^h
APOE ε4 non-carrier			Ref	Ref	Ref	Ref
APOE ε4 heterozygote			0.007 (0.033)	0.000 (0.034)	-0.036 (0.031)	-0.048 (0.034)
APOE ε4 homozygote			-0.001 (0.052)	-0.012 (0.054)	-0.043 (0.052)	-0.127 (0.057) ^*
Educational attainment				0.005 (0.006)	0.008 (0.005)
Smoking				-0.012 (0.031)	-0.021 (0.027)
Marital status (referent: married)				-0.031 (0.039)	-0.029 (0.033)
Clinical cognitive status
CN				Ref	Ref
MCI				-0.017 (0.029)	-0.044 (0.026)
Dementia				0.036 (0.035)	-0.029 (0.034)
CSF Aβ₁₋₄₂					0.205 (0.029) ^***
CSF t-Tau					0.474 (0.137) ^***
CSF p-Tau					0.083 (0.124)
The p-Tau/Aβ₁₋₄₂ ratio						2.268 (0.481)^***
Size	1017	1017	1012	1005	997	1012
Observations	1752	1752	1742	1731	1691	1742
AIC	1747	1754	1730	1745	1406	1682

^aModel 1 included age as fixed effects with an additional random slope and intercept for age
^bModel 2 added sex as covariate
^cModel 3 further added race/ethnicity (referent: non-Hispanic white), TREM2 rare variant carrying status (any TREM2 rare variant vs. no TREM2 rare variant), APOE ε4 carrying status (one E4 vs. no E4, two E4 vs. no E4) (fixed effects)
^dModel 4 additionally adjusted educational attainment (continuous), smoking status (ever smoker vs. never smoker), marital status (referent: married), clinical cognitive status (referent: CN)
^eModel 5 additionally controlled for CSF Aβ1–42, CSF t-Tau, CSF p-Tau
^fModel 6 further introduced the p-Tau/Aβ1–42 ratio based on model 3
^gValues are shown as regression coefficient (standard error)
^hAPOE ε4 allele status: APOE ε4 non-carrier, APOE ε2/ε2 or APOE ε2/ε3 or APOE ε3/ε2 or APOE ε3/ε3; APOE ε4 heterozygote, APOE ε3/ε4 or APOE ε2/ε4; APOE ε4 homozygote, APOE ε4/ε4
^*represeted statistically significant. ^*Significant at P < 0.05. ^**Significant at P < 0.01. ^***Significant at P < 0.001
Abbreviations CN, cognitively normal; MCI, mild cognitive impairment; CSF, cerebrospinal fluid; Aβ1–42, amyloid-β1–42; t-Tau, total tau; sTREM2, soluble TREM2

ISSN: 1758-9193