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Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease

Koelewijn, Loes ORCID:, Lancaster, Thomas M. ORCID:, Linden, David ORCID:, Dima, Diana C. ORCID:, Routley, Bethany C., Magazzini, Lorenzo ORCID:, Barawi, Kali, Brindley, Lisa ORCID:, Adams, Rachael, Tansey, Katherine E., Bompas, Aline ORCID:, Tales, Andrea, Bayer, Antony ORCID: and Singh, Krish ORCID: 2019. Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer's disease. eLife 8 , e36011. 10.7554/eLife.36011

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We studied resting-state oscillatory connectivity using magnetoencephalography in healthy young humans (N = 183) genotyped for APOE-ɛ4, the greatest genetic risk for Alzheimer’s disease (AD). Connectivity across frequencies, but most prevalent in alpha/beta, was increased in APOE-ɛ4 in a set of mostly right-hemisphere connections, including lateral parietal and precuneus regions of the Default Mode Network. Similar regions also demonstrated hyperactivity, but only in gamma (40–160 Hz). In a separate study of AD patients, hypoconnectivity was seen in an extended bilateral network that partially overlapped with the hyperconnected regions seen in young APOE-ɛ4 carriers. Using machine-learning, AD patients could be distinguished from elderly controls with reasonable sensitivity and specificity, while young APOE-e4 carriers could also be distinguished from their controls with above chance performance. These results support theories of initial hyperconnectivity driving eventual profound disconnection in AD and suggest that this is present decades before the onset of AD symptomology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Cardiff University Brain Research Imaging Centre (CUBRIC)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This article is distributed under the terms of the Creative Commons Attribution License.
Publisher: eLife Sciences Publications
ISSN: 2050-084X
Date of First Compliant Deposit: 7 May 2019
Date of Acceptance: 17 April 2019
Last Modified: 11 Oct 2023 20:38

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