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

BackgroundWhile the precuneus role in integrating diverse brain functions and its early involvement in Alzheimers Disease (AD) is well established, the differential impact of AD pathology on its subregions is poorly understood. This study aims to delineate the differential involvement and vulnerability of these subdivisions in the early stages of AD progression. MethodsWe conducted a resting-state functional connectivity analysis in 32 asymptomatic carriers of the PSEN1 E280A mutation for familial Alzheimers disease and compared them to 25 non-carrier familial controls. Seed-based functional connectivity analysis was applied to the precuneus and its subregions. ResultsAmong carriers, the 7Am subregion exhibited the most pronounced statistical differences, consisting of increased connectivity with the entorhinal cortex, superior temporal gyrus, insula-operculum, dorsolateral prefrontal cortex, and somatosensory areas. The POS2 subregion further significantly decreased its connectivity with the anterior insula and dorsolateral prefrontal cortex. Higher MoCA scores correlated with increased within and between precuneus and frontoparietal network connectivity, alongside decreased connectivity between 7Pm, PCV, POS2, and the medial temporal lobe. Additionally, the 7m subregion displayed significantly higher connectivity with medial and dorsolateral prefrontal regions. ConclusionsOur findings highlight the importance of subregional analysis in precuneus connectivity, uncovering patterns that do not exist when the precuneus is treated as a single region of interest--as is common in neuroimaging studies. Notably, even in preclinical stages of Alzheimers disease, early connectivity changes are evident, supporting their potential as biomarkers of disease progression. These results also point to the distinct involvement and vulnerability of precuneus subdivisions during the initial phases of AD.