Oscillatory Hyperactivity and Hyperconnectivity in Young -ɛ4 Carriers and Hypoconnectivity in Alzheimer's Disease

Overview

Journal Elife

Specialty Biology

Date 2019 May 1

PMID 31038453

Citations 50

Authors

Loes Koelewijn

Thomas M Lancaster

David Linden

Diana C Dima

Bethany C Routley

Lorenzo Magazzini

Kali Barawi

Lisa Brindley

Rachael Adams

Katherine E Tansey

Aline Bompas

Andrea Tales

Antony Bayer

Krish Singh

Affiliations

Soon will be listed here.

Abstract

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.

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