Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multimodal imaging investigation

Neurobiol Aging. 2019 Jan;73:82-91. doi: 10.1016/j.neurobiolaging.2018.08.026. Epub 2018 Sep 22.


Young adult APOE-ε4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (one half of whom were APOE-ε4 carriers; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. The parahippocampal cingulum bundle (PHCB)-which links the pDMN and the medial temporal lobe-was manually delineated in individual participants using deterministic tractography. Measures of tract microstructure (mean diffusivity and fractional anisotropy) were then extracted from these tract delineations. APOE-ε4 carriers had lower mean diffusivity and higher fractional anisotropy relative to noncarriers in PHCB, but not in a control tract (the inferior longitudinal fasciculus). Furthermore, PHCB microstructure was selectively associated with pDMN (and medial temporal lobe) activity during a scene discrimination task known to be sensitive to Alzheimer's disease. These findings are consistent with a lifespan view of Alzheimer's disease risk, where early-life, connectivity-related changes in specific, vulnerable "hubs" (e.g., pDMN) lead to increased neural activity. Critically, such changes may reflect reduced network efficiency/flexibility in APOE-ε4 carriers, which in itself may portend a faster decline in connectivity over the lifespan and ultimately trigger early amyloid-β deposition in later life.

Keywords: Alzheimer's disease; Default mode network; Diffusion MRI; Medial temporal lobe; Scene processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / etiology
  • Anisotropy
  • Apolipoprotein E4 / genetics*
  • Diffusion Magnetic Resonance Imaging
  • Diffusion Tensor Imaging / methods
  • Female
  • Gyrus Cinguli / diagnostic imaging*
  • Gyrus Cinguli / pathology
  • Gyrus Cinguli / physiopathology*
  • Heterozygote*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Multimodal Imaging
  • Neuroimaging
  • Parahippocampal Gyrus / diagnostic imaging*
  • Parahippocampal Gyrus / pathology
  • Parahippocampal Gyrus / physiopathology*
  • Risk
  • Temporal Lobe / diagnostic imaging*
  • Temporal Lobe / pathology
  • Temporal Lobe / physiopathology*
  • Young Adult


  • Apolipoprotein E4