resting-state network disruption and apoe genotype in alzheimers disease a lagged functional connectivity study静息状态的网络中断和载脂蛋白e基因型在阿尔茨海默病滞后功能连通性的研究.pdfVIP

Resting-State Network Disruption and APOE Genotype in Alzheimer’s Disease: A lagged Functional Connectivity Study 1 1 1 1 2 Leonides Canuet *, Ivan Tellado , Veronica Couceiro , Carmen Fraile , Lucia Fernandez-Novoa , 3 3 1,2 Ryouhei Ishii , Masatoshi Takeda , Ramon Cacabelos 1 EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic Medicine, Corunna, Spain, 2 EuroEspes Biotechnology Division (Ebiotec), Institute for CNS Disorders and Genomic Medicine, Corunna, Spain, 3 Department of Psychiatry, Osaka University Graduate School of Medicine, Suita city, Osaka, Japan Abstract Background: The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to Alzheimer’s disease (AD) and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called ‘‘lagged phase synchronization’’. Methodology/Principal Findings: Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to nonc