Individual Correspondence of Amyloid-β and Intrinsic Connectivity in the Posterior Default Mode Network Across Stages of Alzheimer's Disease

In Alzheimer's disease (AD), amyloid-beta (A beta) pathology and intrinsic functional connectivity (iFC) interact. Across stages of AD, we expected individual spatial correspondence of A beta and iFC to reveal both A beta accumulation and its detrimental effects on iFC. We used resting-state functional magnetic imaging and A beta imaging in a cross-sectional sample of 90 subjects across stages of AD and healthy older adults. Global and local correspondence of A beta and iFC were assessed within the posterior default mode network (pDMN) by within-subject voxel-wise correlations. Beginning at preclinical stages, global A beta-iFC correspondence was positive for the whole pDMN, showing that A beta accumulates in areas of high connectivity, and reached a plateau at prodromal stages. Starting at preclinical stages, local correspondence was negative in network centers, indicating that A beta reduces connectivity of the pDMN as a function of local plaque concentration, and peaked at prodromal stages. Positive global correspondence suggests that A beta accumulation progresses along iFC, with this effect starting in preclinical stages, and being constant along clinical periods. Negative local correspondence suggests detrimental effects of A beta on iFC in network centers, starting at preclinical stages, and peaking when first symptoms appear. Data reveal a complex trajectory of A beta and iFC correspondence, affecting both A beta accumulation and iFC impairments.