Resting-state network disruption and APOE genotype in Alzheimer's disease

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Details zur Publikation

Untertitel: a lagged functional connectivity study
Autorenliste: Canuet L
Verlag: Public Library of Science
Jahr der Veröffentlichung: 2012
Zeitschrift: PLoS ONE (1932-6203)
Bandnummer: 7
Heftnummer: 9
Erste Seite: e46289
Seitenumfang: 12
ISSN: 1932-6203
eISSN: 1932-6203
Sprachen: Englisch-Vereinigtes Königreich (EN-GB)


Beschreibung

BACKGROUND: The apolipoprotein E epsilon 4 (APOE-4) is associated with a
genetic vulnerability to Alzheimer's disease (AD) and with AD-related
abnormalities in cortical rhythms. However, it is unclear whether APOE-4
is linked to a specific pattern of intrinsic functional disintegration
of the brain after the development of the disease or during its
different stages. This study aimed at identifying spatial patterns and
effects of APOE genotype on resting-state oscillations and functional
connectivity in patients with AD, using a physiological connectivity
index called "lagged phase synchronization". METHODOLOGY/PRINCIPAL
FINDINGS: Resting EEG was recorded during awake, eyes-closed state in
125 patients with AD and 60 elderly controls. Source current density and
functional connectivity were determined using eLORETA. Patients with AD
exhibited reduced parieto-occipital alpha oscillations compared with
controls, and those carrying the APOE-4 allele had reduced alpha
activity in the left inferior parietal and temporo-occipital cortex
relative to noncarriers. There was a decreased alpha2 connectivity
pattern in AD, involving the left temporal and bilateral parietal
cortex. Several brain regions exhibited increased lagged phase
synchronization in low frequencies, specifically in the theta band,
across and within hemispheres, where temporal lobe connections were
particularly compromised. Areas with abnormal theta connectivity
correlated with cognitive scores. In patients with early AD, we found an
APOE-4-related decrease in interhemispheric alpha connectivity in
frontal and parieto-temporal regions. CONCLUSIONS/SIGNIFICANCE: In
addition to regional cortical dysfunction, as indicated by abnormal
alpha oscillations, there are patterns of functional network disruption
affecting theta and alpha bands in AD that associate with the level of
cognitive disturbance or with the APOE genotype. These functional
patterns of nonlinear connectivity may potentially represent
neurophysiological or phenotypic markers of AD, and aid in early
detection of the disorder.


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