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Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer’s disease
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Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer’s disease
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Journal Article
Oscillatory hyperactivity and hyperconnectivity in young APOE-ɛ4 carriers and hypoconnectivity in Alzheimer’s disease
2019
Overview
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.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Age
/ Aged
/ Alzheimer Disease - diagnostic imaging
/ Alzheimer Disease - genetics
/ Alzheimer Disease - metabolism
/ Alzheimer Disease - pathology
/ APOE-ɛ4
/ Apolipoprotein E4 - genetics
/ Apolipoprotein E4 - metabolism
/ Datasets
/ Dementia
/ Elderly
/ Female
/ Genetic Predisposition to Disease
/ Genotype
/ Humans
/ Image Processing, Computer-Assisted
/ Magnetoencephalography - methods
/ Male
/ Proteins
