Effect of APOE ε4 Status on Intrinsic Network Connectivity in Cognitively Normal Elderly Subjects

Arch Neurol. 2011 Sep;68(9):1131-6. doi: 10.1001/archneurol.2011.108. Epub 2011 May 9.


Objective: To examine default mode and salience network functional connectivity as a function of APOE ε4 status in a group of cognitively normal age-, sex-, and education-matched older adults.

Design: Case-control study.

Subjects: Fifty-six cognitively normal APOE ε4 carriers and 56 age-, sex- and education-matched cognitively normal APOE ε4 noncarriers.

Main outcome measure: Alterations in in-phase default mode and salience network connectivity in APOE ε4 carriers compared with APOE ε4 noncarriers ranging from 63 to 91 years of age.

Results: A posterior cingulate seed revealed decreased in-phase connectivity in regions of the posterior default mode network that included the left inferior parietal lobe, left middle temporal gyrus, and bilateral anterior temporal lobes in the ε4 carriers relative to APOE ε4 noncarriers. An anterior cingulate seed showed greater in-phase connectivity in the salience network including the cingulate gyrus, medial prefrontal cortex, bilateral insular cortex, striatum, and thalamus in APOE ε4 carriers vs noncarriers. There were no groupwise differences in brain anatomy.

Conclusions: The observation of functional alterations in default mode and salience network connectivity in the absence of structural changes between APOE ε4 carriers and noncarriers suggests that alterations in connectivity may have the potential to serve as an early biomarker.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apolipoprotein E4 / genetics*
  • Brain / physiology*
  • Case-Control Studies
  • Cognition / physiology*
  • Cohort Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Net / physiology*
  • Neuropsychological Tests
  • Prospective Studies
  • Protein Isoforms / genetics*


  • Apolipoprotein E4
  • Protein Isoforms