title: Influence of the APOE ε4 allele and mild cognitive impairment diagnosis in the disruption of the MEG resting state functional connectivity in sources space.
abstract: The apolipoprotein E (APOE) ε4 allele constitutes the major genetic risk for the development of late onset Alzheimer's disease (AD). However, its influence on the neurodegeneration that occurs in early AD remains unresolved. In this study, the resting state magnetoencephalography(MEG) recordings were obtained from 27 aged healthy controls and 36 mild cognitive impairment (MCI) patients. All participants were divided into carriers and non-carriers of the ε4 allele. We have calculated the functional connectivity (FC) in the source space along brain regions estimated using the Harvard-Oxford atlas and in the classical bands. Then, a two way ANOVA analysis (diagnosis and APOE) was performed in each frequency band. The diagnosis effect consisted of a diminished FC within the high frequency bands in the MCI patients, affecting medial temporal and parietal regions. The APOE effect produced a decreased long range FC in delta band in ε4 carriers. Finally, the interaction effect showed that the FC pattern of the right frontal-temporal region could be reflecting a compensatory/disruption process within the ε4 allele carriers. Several of these results correlated with cognitive decline and neuropsychological performance. The present study characterizes how the APOE ε4 allele and MCI status affect the brain's functional organization by analyzing the FC patterns in MEG resting state in the sources space. Therefore a combination of genetic, neuropsychological, and neurophysiological information might help to detect MCI patients at higher risk of conversion to AD and asymptomatic subjects at higher risk of developing a manifest cognitive deterioration.
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain Department of Basic Psychology II, Complutense University of Madrid, Spain Department of Applied Physics III, Faculty of Physics, Complutense University of Madrid, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cuesta
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain Department of Applied Physics III, Faculty of Physics, Complutense University of Madrid, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Garcés
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: Nazareth P
authors.initials: NP
authors.lastname: Castellanos
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain Department of Basic Psychology II, Complutense University of Madrid, Spain.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: López
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Aurtenetxe
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bajo
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain.
authors.forename: José Angel
authors.initials: JA
authors.lastname: Pineda-Pardo
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bruña
authors.affiliation: Memory Decline Prevention Center, Ayuntamiento de Madrid, Spain.
authors.forename: Antonio García
authors.initials: AG
authors.lastname: Marín
authors.affiliation: Seniors Center of the District of Chamartin, Madrid, Spain.
authors.forename: Marisa
authors.initials: M
authors.lastname: Delgado
authors.affiliation: Laboratory of Psychoneuroendocrinology and Molecular Genetics, Biomedical Research Foundation, Clínico San Carlos Hospital, Madrid, Spain Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Barabash
authors.affiliation: Laboratory of Psychoneuroendocrinology and Molecular Genetics, Biomedical Research Foundation, Clínico San Carlos Hospital, Madrid, Spain Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Ancín
authors.affiliation: Laboratory of Psychoneuroendocrinology and Molecular Genetics, Biomedical Research Foundation, Clínico San Carlos Hospital, Madrid, Spain Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Cabranes
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain Department of Psychiatry, Faculty of Medicine, Complutense University of Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Del Pozo
authors.affiliation: Department of Applied Physics III, Faculty of Physics, Complutense University of Madrid, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Sancho
authors.affiliation: Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain Neurology Department, San Carlos University Hospital, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Marcos
authors.affiliation: Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Complutense University of Madrid and Technical University of Madrid, Spain Department of Basic Psychology II, Complutense University of Madrid, Spain Institute of Sanitary Investigation (IdISSC), San Carlos University Hospital, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Maestú
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D058256:Brain Waves; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D012146:Rest
chemical_list: D053327:Apolipoprotein E4
keywords: APOE ε4; Aging; functional connectivity; magnetoencephalography; mild cognitive impairment; source analysis