Table 3. Baseline CSF biomarkers as predictors of the difference between the ADAD mutation carriers and non-carriers in the baseline level and intra-individual rate of change of imaging, clinical and cognitive measures.

Linear mixed effects models were used to estimate the amount of change in imaging, clinical and cognitive measures per unit change in CSF biomarkers. Fixed effects included in the models were biomarker baseline level, mutation status (MC or NC), time, and all possible two-way or three way-interaction among the fixed effects. Baseline age, sex, years of education, APOE ε4 status and their interaction with mutation status were considered as covariates, but only those covariates that were significant were retained in the models. Random effects included random intercepts for familial clusters, as well as individual random intercept and slope for repeated measures. The results for entorhinal cortical thickness, precuneus thickness, CDR, CDR-SB and MMSE are shown in Supplementary Table 2.

Baseline level		Aβ42 (pg/ml)	Aβ42/Aβ40	tTau (pg/ml)	pTau (pg/ml)	Ng (pg/ml)	SNAP-25 (pg/ml)	VILIP-1 (pg/ml)	YKL-40 (ng/ml)
DIAN cognitive composite	Estimate	0.0003	6.9	−0.002	−0.01	−0.0001	−0.1	−0.002	−0.003
	S.E.	0.00008	1.6	0.0003	0.002	0.00004	0.03	0.0006	0.0007
	p-value	0.0002	<0.0001	<0.0001	<0.0001	0.003	<0.0001	0.0009	0.0004
Amyloid PET SUVR	Estimate	−0.0007	−11.9	0.001	0.01	0.0001	0.05	0.002	0.003
	S.E.	0.00009	1.7	0.0004	0.003	0.00005	0.03	0.0008	0.0008
	p-value	<0.0001	<0.0001	0.0007	0.0001	0.04	N.S.	0.004	0.0003
Hippocampal volume (mm3)	Estimate	0.2	4097.2	−2.2	−16.4	−0.2	−97.1	−2.3	−4.6
	S.E.	0.1	2235.5	0.4	3.1	0.06	39.2	0.9	0.9
	p-value	0.08	0.07	<0.0001	<0.0001	0.008	0.02	0.01	<0.0001
Rate of change		Aβ42 (pg/ml)	Aβ42/Aβ40	tTau (pg/ml)	pTau (pg/ml)	Ng (pg/ml)	SNAP-25 (pg/ml)	VILIP-1 (pg/ml)	YKL-40 (ng/ml)
DIAN cognitive composite	Estimate	0.00009	1.7	−0.0007	−0.005	−0.00007	−0.04	−0.0009	−0.0009
	S.E.	0.00003	0.6	0.0001	0.0009	0.00002	0.01	0.0003	0.0002
	p-value	0.008	0.004	<0.0001	<0.0001	0.007	0.0003	0.007	0.0003
Amyloid PET SUVR	Estimate	−0.00002	−0.2	0.0003	0.002	0.00004	−0.005	0.0003	0.00003
	S.E.	0.00002	0.4	0.0001	0.0006	0.00001	0.009	0.0002	0.0002
	p-value	N.S.	N.S.	0.002	0.009	0.002	N.S.	N.S.	N.S.
Hippocampal volume (mm3)	Estimate	0.2	2662.4	−0.9	−6.1	−0.09	−66.1	−1.3	−1.6
	S.E.	0.03	588.5	0.1	0.9	0.02	13.8	0.3	0.2
	p-value	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001

Abbreviations: Aβ40, amyloid-β 40; Aβ42, amyloid-β 42; ADAD, autosomal dominant Alzheimer disease; CSF, cerebrospinal fluid; CDR, Clinical Dementia Rating; CDR-SB, Clinical Dementia Rating, Sum of Boxes; DIAN, Dominantly Inherited Alzheimer Network; MMSE, Mini-Mental State Examination; Ng, neurogranin; N.S., not significant; PET, positron emission tomography; pTau, phosphorylated tau181; S.E., standard error; SNAP-25, synaptosomal-associated protein-25; SUVR, standardized uptake value ratio; tTau, total tau; VILIP-1, visinin-like protein 1; YKL-40, chitinase-3-like protein 1.