Extended Data Fig. 6: Exploratory analyses testing whether sex affects the association between Aβ and glial reactivity.
From: Microglia modulate Aβ-dependent astrocyte reactivity in Alzheimer’s disease
(a) Association of Aβ PET with plasma GFAP in men (open dots) and women (solid dots) according to MATSPO status (primary sample). n = 101; 50 MA-TSPO (11 males, mean [SD] age of 71.4 [5.7] years) and 51 MA+TSPO (22 males, mean [SD] age of 72.4 [7.2] years). (b) Association of Aβ PET with plasma GFAP in men (open dots) and women (solid dots) according MAsTREM2 status (secondary sample). n = 251; 116 MA-sTREM2 (42 males, mean [SD] age of 65.9 [7.3] years) and 135 MA+sTREM2 (53 males, mean [SD] age of 68.3 [7.2] years). Dots and error bars represent β-estimates and 95% CI, respectively. Additional analysis using TSPO PET as an index of microglial activation demonstrated no significant interaction between sex and Aβ PET on plasma GFAP in either MA-TSPO (β = 0.250, 95% CI -0.340 to 0.841, P = 0.398) or MA+TSPO (β = 0.029, 95% CI -0.479 to 0.537, P = 0.909) individuals. When using CSF sTREM2 as an index of microglial activation, we observed a significant interaction between sex and Aβ PET on plasma GFAP in MA+sTREM2 (β = -0.019, 95% CI -0.030 to −0.007, P = 0.002) but not in MA-sTREM2 individuals (β = -0.003, 95% CI -0.014 to 0.009, P = 0.651). β-estimates and two-sided P-values were derived from linear regression models using standardized biomarker levels. All models were adjusted for age and cognitive status. The interaction models also accounted for the main effects of the interaction terms. For analysis involving CSF sTREM2, Aβ PET was assessed in centiloids, and cohort was also included as a variable for adjustment in regression models. Females were used as the reference group for the abovementioned statistics. Abbreviations: Aβ = amyloid-β; CI = confidence interval; CSF = cerebrospinal fluid; GFAP = glial fibrillary acidic protein; MA = microglial activation; PET = positron emission tomography; sTREM2 = soluble triggering receptor expressed on myeloid cells 2; TSPO = translocator protein.
