Within‐network changes in strength of the default mode network relate to Alzheimer’s Disease biomarkers in APOE e4 carriers

Abstract

AbstractBackgroundResting state functional connectivity measured with MRI (rsfMRI) is disrupted in Alzheimer’s Disease (AD), although reports of rsfMRI changes in adults with the apolipoprotein E (APOE) ε4 genotype (e4+) have been inconsistent. Here, we compare default mode network (DMN) connectivity between e4+ and non‐carriers (e4‐) groups and assess the relationship to AD‐related biomarkers.MethodSixty‐five e4+ (mean age 70.2 ± 4.1; 33 males) and 60 e4‐ (mean age 71.9 ± 4.1; 28 males) subjects underwent a whole‐brain anatomical MPRAGE and a rsfMRI scan. To focus on the DMN, ROIs were placed in the bilateral posterior cingulate cortex (PCC). The most highly correlated voxels between the left and right PCC ROIs were used to calculate left and right PCC rsfMRI z‐maps. Group differences were assessed and mean connectivity in each significant region was correlated with Aβ PET centiloid values and cerebrospinal fluid (CSF) Aβ42/ Aβ40 ratio, phosphorylated‐tau (p‐tau 181), and total‐tau (t‐tau).ResultEight regions showed group differences (p < 0.05; Figure 1). In the e4+ group, right PCC connectivity to the bilateral anterior middle temporal gyri (Figure 1: ROIs 1 and 2) was negatively related to both centiloid score (p < 0.03) and to CSF p‐tau (p < 0.008; Figure 2). Left PCC connectivity to the right anterior middle temporal gyrus was negatively related to centiloid score (r = ‐0.26, p < 0.042) and CSF p‐tau (r = ‐0.31, p < 0.024). Biomarker values in the e4‐ group were not significantly related to connectivity.ConclusionOur findings are consistent with reports of weakened DMN connectivity in e4+ adults and suggest that differences in connectivity strength may be mediated by amyloid or tau deposition.This work was supported by the National Institutes of Health (R01AG022304).