Journal
SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41598-020-80909-7
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Funding
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Fujirebio
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Meso Scale Diagnostics
- NeuroRx Research
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- ADNI clinical sites in Canada
- Foundation for the National Institutes of Health
- Northern California Institute for Research and Education
- Alzheimer's Therapeutic Research Institute at the University of Southern California
- AbbVie
- BioClinica, Inc.
- Eisai Inc.
- F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Lumosity
- Lundbeck
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- Neurotrack Technologies
- Servier
- Transition Therapeutics
- European Union Seventh Framework Programme (FP7/2007-2013) [604102]
- European 'Union's Horizon 2020 research and innovation programme [720270]
- MORPHEMIC Grant [871643]
- Swiss National Science Foundation [32003B_135679, 32003B_159780, CRSK-3_190185]
- Leenaards Foundation
- Roger De Spoelberch Foundation
- Partridge Foundation
- Swiss National Science Foundation (SNF) [CRSK-3_190185, 32003B_159780] Funding Source: Swiss National Science Foundation (SNF)
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The study found that in Mild Cognitive Impairment stage, patients with the ApoE4 gene exhibit different topological properties in cortical thickness covariance networks compared to non-Carriers, indicating certain differences in the organization of brain networks.
The Apolipoprotein E isoform E4 (ApoE4) is consistently associated with an elevated risk of developing late-onset Alzheimer's Disease (AD); however, less is known about the potential genetic modulation of the brain networks organization during prodromal stages like Mild Cognitive Impairment (MCI). To investigate this issue during this critical stage, we used a dataset with a cross-sectional sample of 253 MCI patients divided into ApoE4-positive ('Carriers') and ApoE4-negative ('non-Carriers'). We estimated the cortical thickness (CT) from high-resolution T1-weighted structural magnetic images to calculate the correlation among anatomical regions across subjects and build the CT covariance networks (CT-Nets). The topological properties of CT-Nets were described through the graph theory approach. Specifically, our results showed a significant decrease in characteristic path length, clustering-index, local efficiency, global connectivity, modularity, and increased global efficiency for Carriers compared to non-Carriers. Overall, we found that ApoE4 in MCI shaped the topological organization of CT-Nets. Our results suggest that in the MCI stage, the ApoE4 disrupting the CT correlation between regions may be due to adaptive mechanisms to sustain the information transmission across distant brain regions to maintain the cognitive and behavioral abilities before the occurrence of the most severe symptoms.
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