TY - JOUR T1 - APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF Aβ42 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 17035 LP - 17040 DO - 10.1523/JNEUROSCI.3987-10.2010 VL - 30 IS - 50 AU - Yvette I. Sheline AU - John C. Morris AU - Abraham Z. Snyder AU - Joseph L. Price AU - Zhizi Yan AU - Gina D'Angelo AU - Collin Liu AU - Sachin Dixit AU - Tammie Benzinger AU - Anne Fagan AU - Alison Goate AU - Mark A. Mintun Y1 - 2010/12/15 UR - http://www.jneurosci.org/content/30/50/17035.abstract N2 - Identifying high-risk populations is an important component of disease prevention strategies. One approach for identifying at-risk populations for Alzheimer's disease (AD) is examining neuroimaging parameters that differ between patients, including functional connections known to be disrupted within the default-mode network. We have previously shown these same disruptions in cognitively normal elderly who have amyloid-β (Aβ) plaques [detected using Pittsburgh Compound B (PIB) PET imaging], suggesting neuronal toxicity of plaques. Here we sought to determine if pathological effects of apolipoprotein E ε4 (APOE4) genotype could be seen independent of Aβ plaque toxicity by examining resting state fMRI functional connectivity (fcMRI) in participants without preclinical fibrillar amyloid deposition (PIB−). Cognitively normal participants enrolled in longitudinal studies (n = 100, mean age = 62) who were PIB− were categorized into those with and without an APOE4 allele and studied using fcMRI. APOE4 allele carriers (E4+) differed significantly from E4− in functional connectivity of the precuneus to several regions previously defined as having abnormal connectivity in a group of AD participants. These effects were observed before any manifestations of cognitive changes and in the absence of brain fibrillar Aβ plaque deposition, suggesting that early manifestations of a genetic effect can be detected using fcMRI and that these changes may antedate the pathological effects of fibrillar amyloid plaque toxicity. ER -