Cacciaglia, Raffaele;
Operto, Gregory;
Falcon, Carles;
De Echavarri-Gomez, Jose Maria Gonzalez;
Sanchez-Benavides, Gonzalo;
Brugulat-Serrat, Anna;
Mila-Aloma, Marta;
... Gispert, Juan Domingo; + view all
(2022)
Genotypic effects of APOE-epsilon 4 on resting-state connectivity in cognitively intact individuals support functional brain compensation.
Cerebral Cortex
, Article bhac239. 10.1093/cercor/bhac239.
(In press).
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Abstract
The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer's disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carriers of the ε4 allele. Yet, no study has assessed APOE-ε4 gene-dose effects on rsFC measures, and only a few studies included measures of cognitive performance to aid a clinical interpretation. We assessed the impact of APOE-ε4 on rsFC in a sample of 429 cognitively unimpaired individuals hosting a high number of ε4 homozygotes (n = 58), which enabled testing different models of genetic penetrance. We used independent component analysis and found a reduced rsFC as a function of the APOE-ε4 allelic load in the temporal default-mode and the medial temporal networks, while recessive effects were found in the extrastriate and limbic networks. Some of these results were replicated in a subsample with negative amyloid markers. Interaction with cognitive data suggests that such a network reorganization may support cognitive performance in the ε4-homozygotes. Our data indicate that APOE-ε4 shapes the functional architecture of the resting brain and favor the idea of a network-based functional compensation.
| Type: | Article |
|---|---|
| Title: | Genotypic effects of APOE-epsilon 4 on resting-state connectivity in cognitively intact individuals support functional brain compensation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/cercor/bhac239 |
| Publisher version: | https://doi.org/10.1093/cercor/bhac239 |
| Language: | English |
| Additional information: | © The Author(s) 2022. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Alzheimer’s disease, APOE-ε4, resting-state connectivity, compensation |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10151875 |
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