title: Reelin-immunoreactive neurons in entorhinal cortex layer II selectively express intracellular amyloid in early Alzheimer's disease.
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.
authors.affiliation: Kavli Institute for Systems Neuroscience & Centre for Neural Computation, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: asgeir.kobro-flatmoen@ntnu.no.
authors.forename: Asgeir
authors.initials: A
authors.lastname: Kobro-Flatmoen
authors.affiliation: Kavli Institute for Systems Neuroscience & Centre for Neural Computation, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: anne.nagelhus@ntnu.no.
authors.forename: Anne
authors.initials: A
authors.lastname: Nagelhus
authors.affiliation: Kavli Institute for Systems Neuroscience & Centre for Neural Computation, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: menno.witter@ntnu.no.
authors.forename: Menno P
authors.initials: MP
authors.lastname: Witter
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018728:Entorhinal Cortex / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism*; D055647:Rats, Transgenic; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: Amyloid-β; Hippocampal formation; Neurodegeneration; Neuropathology; Parahippocampal region