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The temporal expression of amyloid precursor protein mRNA in vitro in dissociated hippocampal neuron cultures
M J Strong1, A Svedmyr, D C Gajdusek
1Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
The subunit protein of the neurofibrillary tangle, the core protein of the neuritic plaque, and the amyloid of the cerebrovasculature in Alzheimer disease and normal aging is a unique 42-amino acid protein (amyloid beta-protein), suggesting a common origin for these pathological entities. However, the expression of the amyloid precursor protein mRNA (APP mRNA) from which the amyloid beta-protein is derived varies between specific neuronal populations. To determine the conditions under which neuronal synthesis of amyloid beta-protein might contribute to the formation of these structures, we have studied the temporal pattern of APP mRNA expression in developing fetal rabbit hippocampal neurons in vitro. Using in situ hybridization with a biotinylated riboprobe transcribed from a cDNA which includes the region encoding the amyloid beta-protein, we have observed a developmentally specific pattern of APP mRNA hybridization during neuronal maturation in vitro.
Insights
Alzheimer disease pathology involves amyloid beta-protein. This study observed amyloid precursor protein mRNA expression patterns in developing neurons, revealing a specific temporal pattern during maturation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Alzheimer disease pathology involves neurofibrillary tangles, neuritic plaques, and cerebrovasculature amyloid, all linked to amyloid beta-protein.
- Amyloid precursor protein mRNA (APP mRNA) expression varies among neuronal populations, suggesting differential roles in pathology.
Purpose of the Study:
- To investigate the temporal expression patterns of APP mRNA in developing fetal rabbit hippocampal neurons in vitro.
- To understand the conditions under which neuronal synthesis of amyloid beta-protein may contribute to Alzheimer disease-related structures.
Main Methods:
- Utilized in situ hybridization with a biotinylated riboprobe targeting APP mRNA.
- Studied developing fetal rabbit hippocampal neurons cultured in vitro.
Main Results:
- Observed a developmentally specific pattern of APP mRNA hybridization during neuronal maturation in vitro.
- Demonstrated that APP mRNA expression is temporally regulated during neuronal development.
Conclusions:
- Neuronal synthesis of amyloid beta-protein is subject to developmental regulation.
- The findings suggest a link between developmental expression patterns and the formation of Alzheimer disease pathological entities.