Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer’s disease
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INTRODUCTION: The longitudinal trajectories of functional brain dynamics and the impact of genetic risk factors in individuals at risk for Alzheimer's disease are poorly understood. METHODS: In a large-scale monocentric cohort of 224 amyloid stratified individuals at risk for Alzheimer's disease, default mode network (DMN) resting state functional connectivity (FC) was investigated between two serial time points across 2 years. RESULTS: Widespread DMN FC changes were shown in frontal and posterior areas, as well as in the right hippocampus. There were no cross-sectional differences, however, apolipoprotein E ε4 (APOE ε4) carriers demonstrated slower increase in FC in frontal lobes. There was no impact of individual brain amyloid load status. DISCUSSION: For the first time, we demonstrated that the pleiotropic biological effect of the APOE ε4 allele impacts the dynamic trajectory of the DMN during aging. Dynamic functional biomarkers may become useful surrogate outcomes for the development of preclinical targeted therapeutic interventions.
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Genetic risk factors with pleiotropic effects, such as APOE ε4, affect default mode network trajectories in cognitively healthy individuals at risk for AD.
“Very recently, it was shown that genetic risk factors with a pleiotropic biological effect, such as the APOE ε4 allele, affect the trajectories of the default mode network of cognitively healthy individuals at risk for AD (129,130).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [129]
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Subcortical Anatomy of the Default Mode Network: a functional and structural connectivity studyPreprint
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- Authors
- Chiesa, P. A., Cavedo, E., Vergallo, A., Lista, S., Potier, M., Habert, M., Dubois, B., Thiebaut de Schotten, M., Hampel, H., and the INSIGHT‐preAD study group, & (APMI), F. T. P. M. I.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225 Boulevard de l'hôpital Paris France
- Sorbonne Université (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Corresponding author
- Chiesa, Patrizia A.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2019-05-18
- Volume
- 15
- Issue
- 7
- Pages
- 940-950
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2944824748
- Cited by
- 66
- References
- 68
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 17 · 2020: 13 · 2019: 1
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- HAL (submittedVersion, cc-by-nc)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion, other-oa)
- HAL Portal Artxiker (Hindustan Aeronautics Limited (India)) (submittedVersion)
- HAL (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by-nc-nd)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
- Research Explorer (The University of Manchester) (submittedVersion)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Funders
- AXA Research Fund
- Institut National de la Santé et de la Recherche Médicale (ICM, IHU-A-ICM)
- Agence Nationale de la Recherche (ANR-13-JSV4-0001-01)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- default mode network, resting-state functional connectivity
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Apolipoproteins E, Brain, Brain Mapping, Female, Frontal Lobe, Hippocampus, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Neuropsychological Tests, Temporal Lobe, Cohort Studies
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