Subregional Functional Connectivity of the Precuneus as a Preclinical Biomarker in Alzheimer’s Disease

Introduction The precuneus (Pc) is a central hub integrating diverse brain functions, and it is early involved in Alzheimer’s disease (AD) pathophysiology, yet its subregional vulnerability remains poorly understood. This study aims to delineate the differential involvement and vulnerability of these subdivisions in the early stages of AD. Methods We conducted a resting‐state FC analysis of Pc subregions in 32 cognitively unimpaired carriers of the PSEN1 E280A mutation compared to 25 noncarriers using seed‐based analyses. Results As compared to noncarriers, we found that the group of asymptotic carriers had increased connectivity from the 7Am subregion toward the entorhinal cortex, superior temporal gyrus, insula‐operculum, dlPFC, and somatosensory areas. Moreover, the POS2 subregion significantly decreased connectivity with the anterior insula and dlPFC. Higher MoCA scores correlated with increased connectivity within and between the Pc and frontoparietal networks. Discussion These results reveal distinct patterns of early functional reorganization and support the subregional Pc analysis in identifying sensitive biomarkers for preclinical AD, often overlooked in conventional whole‐region analyses.