Impact of APOE on amyloid and tau accumulation in argyrophilic grain disease and Alzheimer’s disease

Raulin, Ana-Caroline; Doss, Sydney V.; Heckman, Michael G.; Craver, Emily C.; Li, Zonghua; Ikezu, Tadafumi C.; Sekiya, Hiroaki; Liu, Chia-Chen; Martens, Yuka A.; Rosenberg, Cassandra L.; Kuchenbecker, Lindsey A.; DeTure, Michael; Reichard, R. Ross; Nguyen, Aivi T.; Constantopoulos, Eleni; Larsen, Rachel A.; Kounaves, Emmaline K.; Murray, Melissa E.; Dickson, Dennis W.; Petersen, Ronald C.; Bu, Guojun; Kanekiyo, Takahisa

doi:10.1186/s40478-024-01731-0

Acta Neuropathologica Communications

Table 5 Interactions of APOE with tau pathology regarding associations with AD-related molecules

From: Impact of APOE on amyloid and tau accumulation in argyrophilic grain disease and Alzheimer’s disease

	N	No tau pathology: AD-tau ( −), AGD-tau ( −)		AD-tau pathology only AD-tau ( +), AGD-tau ( −)		Mixed tauopathy AD-tau (+ / −), AGD-tau ( +)		APOE x tau pathology interaction
	N	β (95% CI)	P-value	β (95% CI)	P-value	β (95% CI)	P-value	Interaction p-value
APOE2 vs. APOE3 (reference)		APOE2 (N = 21) vs APOE3 (N = 73)		APOE2 (N = 13) vs APOE3 (N = 54)		APOE2 (N = 11) vs APOE3 (N = 27)
Aβ40-TBS	174	0.90 (− 0.20 to 1.99)	0.11	0.12 (− 1.26 to 1.49)	0.86	− 0.72 (− 2.08–0.63)	0.28	0.45
Aβ40-TBSX	188	0.27 (− 0.51 to 1.05)	0.49	− 0.32 (− 1.41 to 0.77)	0.56	− 0.94 (− 1.80, 0.08)	0.034	0.14
Aβ40-FA	188	1.47 (− 3.72 to 6.67)	0.57	1.16 (− 7.28 to 9.61)	0.78	3.05 (− 2.25 to 8.34)	0.25	0.95
Aβ42-TBS	186	0.09 (− 1.38 to 1.56)	0.90	1.52 (− 0.73 to 3.76)	0.18	0.42 (− 1.86 to 2.70)	0.71	0.60
Aβ42-TBSX	192	− 0.19 (− 1.45 to 1.07)	0.77	0.00 (− 1.84 to 1.84)	1.00	− 2.47 (− 4.64, 0.30)	0.027	0.11
Aβ42-FA	197	1.86 (− 12.81 to 16.52)	0.80	6.19 (− 11.78 to 24.17)	0.49	− 3.16 (− 25.26 to 18.93)	0.77	0.77
apoE-TBS	196	0.52 (0.02 to 1.03)	0.042	0.56 (− 0.02 to 1.15)	0.059	0.75 (0.18to 1.32)	0.012	0.90
apoE-TBSX	194	− 0.04 (− 0.27 to 0.18)	0.70	− 0.17 (− 0.43 to 0.08)	0.18	− 0.19 (− 0.52 to 0.14)	0.26	0.64
apoE-FA	197	0.17 (− 0.59 to 0.93)	0.66	0.06 (− 0.88 to 1.00)	0.90	0.07 (− 0.81 to 0.95)	0.87	0.89
tTau-TBS	176	− 7.27 (-14.55, 0.00)	0.050	3.50 (-6.45 to 13.44)	0.48	− 1.75 (− 12.13 to 8.64)	0.73	0.18
tTau-TBSX	194	− 0.05 (− 0.25 to 0.16)	0.67	0.08 (− 0.24 to 0.39)	0.63	− 0.19 (− 0.46 to 0.09)	0.18	0.51
tTau-FA	201	− 0.05 (− 0.30 to 0.20)	0.69	0.35 (0.10 to 0.60)	0.007	0.25 (− 0.06 to 0.55)	0.11	0.061
pTau181-TBS	194	− 0.01 (− 0.25 to 0.22)	0.92	− 0.08 (− 0.41 to 0.24)	0.61	− 0.34 (− 0.72 to 0.04)	0.075	0.23
pTau181-TBSX	194	− 0.19 (− 0.38 to 0.01)	0.058	0.10 (− 0.10 to 0.31)	0.32	− 0.20 (− 0.46 to 0.06)	0.13	0.10
pTau181-FA	192	− 0.24 (− 0.44, 0.03)	0.023	0.46 (− 0.18 to 1.10)	0.15	0.24 (− 0.14 to 0.62)	0.21	0.065
APOE4 vs. APOE3 (reference)		APOE4 (N = 20) vs APOE3 (N = 73)		APOE4 (N = 115) vs APOE3 (N = 54)		APOE4 (N = 13) vs APOE3 (N = 27)
Aβ40-TBS	267	0.48 (− 0.52 to 1.49)	0.34	0.85 (− 0.07 to 1.77)	0.069	− 0.63 (− 1.98 to 0.71)	0.34	0.50
Aβ40-TBSX	292	0.12 (− 0.68 to 0.93)	0.76	1.31 (0.51 to 2.11)	0.002	− 0.14 (− 0.74 to 0.47)	0.65	0.049
Aβ40-FA	290	7.21 (− 0.05 to 14.48)	0.052	14.15 (7.47 to 20.83)	< 0.001	1.44 (− 3.49 to 6.37)	0.56	0.088
Aβ42-TBS	289	2.68 (1.34 to 4.02)	< 0.001	1.08 (0.19 to 1.96)	0.017	2.09 (− 0.13 to 4.32)	0.064	0.11
Aβ42-TBSX	293	2.18 (0.80 to 3.57)	0.002	1.07 (0.36 to 1.79)	0.004	2.98 (0.99 to 4.97)	0.004	0.10
Aβ42-FA	303	21.79 (6.52 to 37.07)	0.006	9.15 (1.22 to 17.07)	0.024	26.52 (7.49 to 45.55)	0.008	0.16
apoE-TBS	303	− 0.29 (− 0.80 to 0.22)	0.26	− 0.33 (− 0.65, 0.02)	0.036	0.27 (− 0.25 to 0.79)	0.30	0.32
apoE-TBSX	296	− 0.03 (− 0.28 to 0.22)	0.82	0.22 (0.08 to 0.36)	0.002	0.02 (− 0.27 to 0.31)	0.89	0.087
apoE-FA	302	0.31 (− 0.46 to 1.08)	0.43	1.41 (0.82 to 2.01)	< 0.001	0.91 (− 0.15 to 1.96)	0.091	0.085
tTau-TBS	278	− 0.34 (− 7.37 to 6.69)	0.92	1.01 (− 4.32 to 6.34)	0.71	− 1.23 (− 10.56 to 8.09)	0.79	0.85
tTau-TBSX	296	0.01 (− 0.21 to 0.23)	0.91	− 0.09 (− 0.26 to 0.07)	0.25	0.05 (− 0.23 to 0.33)	0.71	0.76
tTau-FA	308	0.02 (− 0.23 to 0.27)	0.89	− 0.09 (− 0.23 to 0.05)	0.19	− 0.08 (− 0.38 to 0.22)	0.60	0.76
pTau181-TBS	297	− 0.11 (− 0.36 to 0.13)	0.37	− 0.03 (− 0.20 to 0.15)	0.77	− 0.18 (− 0.42 to 0.07)	0.16	0.79
pTau181-TBSX	295	− 0.23 (− 0.44, 0.03)	0.024	0.09 (− 0.02 to 0.21)	0.10	− 0.22 (− 0.44 to 0.00)	0.052	0.004
pTau181-FA	296	0.18 (− 0.04–0.40)	0.12	0.60 (0.24 to 0.97)	0.001	0.04 (− 0.33 to 0.40)	0.85	0.067

β Regression coefficient; CI Confidence interval. β values, 95% CIs, and p-values result from linear regression models that were adjusted for age and sex. β values are interpreted as the difference in means of the given AD-related molecule on the square root (tTau-TBS), cube root (apoE-TBSX, tTau-TBSX, tTau-FA), or natural logarithm scale (Aβ40-TBS, Aβ40-TBSX, Aβ40-FA, Aβ42-TBS, Aβ42-TBSX, Aβ42-FA, apoE-TBS, apoE-FA, pTau181-TBS, pTau181-TBSX, pTau181-FA) in comparison to the APOE3 group. For tests of interaction, models were additionally adjusted for APOE group and the interaction between combination of AD-tau and AGD-tau pathology and APOE group. P-values < 0.01 were considered as statistically significant after applying a Bonferroni correction for multiple testing separately for each fraction and each pair-wise comparison between APOE groups; significant associations are underlined, and significant interactions are shown in bold

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