The role of Apolipoprotein D in normal and pathological aging in Drosophila

Julien A. Muffat, David W. Walker, Seymour Benzer

Human Apolipoprotein D (hApoD) is upregulated 350% in the CSF of patients with Alzheimer's disease. The protein appears to be secreted by astrocytes and other reactive glial cells, and is recruited to sites of neuronal injury and amyloid deposition. As ApoD and its homologs are small hydrophilic molecules capable of carrying a single hydrophobic ligand (such as cholesterol), they may play a role in neuronal maintenance and survival, either by carrying trophic factors or essential building blocks of cell membranes.

Drosophila Glial Lazarillo (Glaz) shares 40% of its protein sequence with hApoD. Preliminary results of in situ hybridization in adult Drosophila indicate that thoracic muscles and the nervous system are the main organs expressing Glaz. We have shown that 10-fold overexpression of the Glaz gene, using the UAS/GAL4 bipartite system, results in 30% longer lifespan for Drosophila. This overexpression also enhances stress resistance, as assessed by starvation, dessication, heat shock or hyperoxia. Such flies also contain 20% less fat than controls. By the use of various tissue-specific driver lines, we observed that overexpression in vertical muscles and parts of the nervous system is sufficient to produce the beneficial effects.