Reelin-immunoreactive neurons in entorhinal cortex layer II selectively express intracellular amyloid in early Alzheimer's disease

Neurobiol Dis. 2016 Sep:93:172-83. doi: 10.1016/j.nbd.2016.05.012. Epub 2016 May 16.

Abstract

The onset of Alzheimer's disease (AD) is associated with subtle pathological changes including increased intracellular expression of amyloid-β (Aβ). A structure affected particularly early in the course of AD is the entorhinal cortex, where neuronal death in layer II is observed already at initial stages. Neurons in EC-layer II, particularly those that express the protein Reelin, give rise to projections to the hippocampal dentate gyrus and this projection shows severe loss of synaptic contacts during early-stage AD. Given this anatomical specificity, we sought to determine whether increased intracellular expression of Aβ is selectively associated with Reelin-immunoreactive neurons in layer II of the entorhinal cortex. Here we report that in a transgenic rat model, which mimics the onset and distribution of extracellular amyloid deposits seen in human AD subjects, expression of intracellular Aβ in entorhinal layer II selectively occurs in Reelin-immunoreactive neurons during the early, pre-plaque stage. This Reelin-Aβ association is also present in human subjects with AD-related pathological changes, even in early disease stages. These findings strongly indicate that Reelin-immunoreactive neurons in entorhinal layer II play a crucial role during the initial stages of AD, and may therefore lead to refined hypotheses concerning the origin of this devastating condition.

Keywords: Amyloid-β; Hippocampal formation; Neurodegeneration; Neuropathology; Parahippocampal region.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cytoplasm / metabolism
  • Entorhinal Cortex / metabolism*
  • Entorhinal Cortex / pathology
  • Extracellular Matrix Proteins / metabolism
  • Hippocampus / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Plaque, Amyloid / metabolism*
  • Rats, Transgenic
  • Reelin Protein
  • Serine Endopeptidases / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Reelin Protein
  • Reln protein, rat
  • RELN protein, human
  • Serine Endopeptidases