Neuritic Deposits of Amyloid-beta Peptide in a Subpopulation of Central Nervous System-derived Neuronal Cells.
From: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4970, USA.
Molecular and cellular biology
- Publish Date: Jul 2006
- ISSN: 0270-7306
- Volume: 26
- Issue: 13
- Pages: 4982-97
- Medium: Print
- Language: English
- Citation (JAMA): Muresan Zoia, Muresan Virgil, et al. Neuritic Deposits of Amyloid-beta Peptide in a Subpopulation of Central Nervous System-derived Neuronal Cells.. Mol. Cell. Biol. Jul 2006;26:4982-97
Abstract
Our goal is to understand the pathogenesis of amyloid-beta (Abeta) deposition in the Alzheimer’s disease (AD) brain. We established a cell culture system where central nervous system-derived neuronal cells (CAD cells) produce and accumulate within their processes large amounts of Abeta peptide, similar to what is believed to occur in brain neurons, in the initial phases of AD. Using this system, we show that accumulation of Abeta begins within neurites, prior to any detectable signs of neurodegeneration or abnormal vesicular transport. Neuritic accumulation of Abeta is restricted to a small population of neighboring cells that express normal levels of amyloid-beta precursor protein (APP) but show redistribution of BACE1 to the processes, where it colocalizes with Abeta and markers of late endosomes. Consistently, cells that accumulate Abeta appear in isolated islets, suggesting their clonal origin from a few cells that show a propensity to accumulate Abeta. These results suggest that Abeta accumulation is initiated in a small number of neurons by intracellular determinants that alter APP metabolism and lead to Abeta deposition and neurodegeneration. CAD cells appear to recapitulate the biochemical processes leading to Abeta deposition, thus providing an experimental in vitro system for studying the molecular pathobiology of AD.
Mesh Headings (Keywords): Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Protein, Animals, Apoptosis, Aspartic Endopeptidases, Cells, Cultured, Central Nervous System, Endopeptidases, Mice, Necrosis, Neurites, Neurons
Check for Full Text / PubMed Unique Identifier (PMID): 16782885
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