期刊
NEUROBIOLOGY OF DISEASE
卷 93, 期 -, 页码 172-183出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2016.05.012
关键词
Neurodegeneration; Neuropathology; Amyloid-beta; Hippocampal formation; Parahippocampal region
资金
- Central Norway Regional Health Authority [46056620]
- Kavli Foundation
- Norwegian Research Council Centre of Excellence and Equipment Grants [145993, 181676]
The onset of Alzheimer's disease (AD) is associated with subtle pathological changes including increased intracellular expression of amyloid-beta (A(beta). 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 A beta 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 A beta in entorhinal layer II selectively occurs in Reelin-immunoreactive neurons during the early, pre-plaque stage. This Reelin-A beta 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. (C) 2016 The Authors. Published by Elsevier Inc.
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