Human Apolipoprotein E Isoform‐Specific Differences in Neuronal Sprouting in Organotypic Hippocampal Culture

• Published in: Journal of neurochemistry 1999-12, Vol.73 (6), p.2613-2616
• Main Authors: Teter, B., Xu, P.‐T., Gilbert, J. R., Roses, A. D., Galasko, D., Cole, G. M.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Apolipoprotein E; Apolipoprotein E3; Apolipoprotein E4; Apolipoproteins E - biosynthesis; Apolipoproteins E - genetics; Apolipoproteins E - physiology; Biological and medical sciences; Culture Media, Conditioned; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Hippocampus - cytology; Hippocampus - metabolism; Humans; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mossy Fibers, Hippocampal - metabolism; Mossy Fibers, Hippocampal - ultrastructure; Nerve Degeneration; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurite sprouting; Neurology; Organ Culture Techniques; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Transgenic mice
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0732613.x

: The apolipoprotein E (ApoE) ε4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease. A role for ApoE is implicated in regeneration of synaptic circuitry after neural injury. In the in vitro mouse organotypic hippocampal slice culture system, we previously showed that cultures derived from ApoE‐knockout mice are defective in mossy fiber sprouting into the dentate gyrus molecular layer. This sprouting defect was rescued in cultures from transgenic mice expressing ApoE3 under the control of the human promoter and in ApoE‐knockout cultures treated with ApoE3‐conditioned media. Although the ApoE3 transgene fully restored sprouting, ApoE4 restored sprouting to only 58% of ApoE3 levels. These data indicate that ApoE isoform‐specific effects on neuroregeneration may contribute to its genetic risk for Alzheimer's disease.