In vivo characterization of the early states of the amyloid-beta network

Brain. 2013 Jul;136(Pt 7):2239-52. doi: 10.1093/brain/awt146.

Abstract

Alzheimer's disease is a neurodegenerative disease that is associated with the abnormal accumulation of amyloid-β. Much is known about regional brain atrophy in Alzheimer's disease, yet our knowledge about the network nature of Alzheimer's disease-associated amyloid-β accumulation is limited. We use stepwise connectivity analysis of Pittsburgh Compound B positron emission tomography images to reveal the network properties of amyloid-β deposits in normal elderly subjects and clinical patients with Alzheimer's disease. We found that amyloid-β accumulation in the medial temporal lobe is associated with accumulation in cortical regions such as orbitofrontal, lateral temporal and precuneus/posterior cingulate cortices in Alzheimer's disease. In normal subjects, there was a predominant association between amyloid-β deposits in the hippocampus and the midline prefrontal/orbitofrontal regions, even in those with very low amyloid-β burden. Moreover, the orbitofrontal cortex, amygdala nucleus and hippocampus exhibit hub properties in the amyloid-β network that may be critical to understanding the putative spreading mechanisms of Alzheimer's disease pathology in early stages.

Keywords: Alzheimer’s disease; amyloid; early stages; graph theory; network.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Brain Mapping*
  • Carbon Isotopes
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / blood supply
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / pathology
  • Oxygen / blood
  • Positron-Emission Tomography
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Carbon Isotopes
  • Thiazoles
  • Oxygen