P1‐034: A role for lithium in rescuing amyloid beta pathology in an inducible drosophila model of Alzheimer's disease

Adesakin, Oyinkan A.; Kerr, Fiona; Partridge, Linda

Abstract

Background
Alzheimer's disease (AD) is the leading cause of dementia in the ageing population. Amyloid beta (Ab) accumulation, which occurs as a result of the amyloidogenic processing of amyloid precursor protein (APP), is thought to initiate the pathogenesis of AD, eventually leading to neuronal cell death. Previously, we developed an adult-onset Drosophila model of AD. Mutant Ab42 accumulation led to increased mortality and neuronal dysfunction in the adult flies. Furthermore, we showed that lithium reduced Ab42 protein, but not mRNA, by causing a reduction in protein synthesis in Drosophila, and thus was able to rescue Ab42-induced toxicity. We found that at both low and high doses tested, lithium rescued the locomotory defects induced by Ab42, but it rescued lifespan only at lower doses, suggesting that long-term, high-dose lithium treatment may have induced toxicity.

Methods
We carried out some microarray analyses in Drosophila expressing Ab42 with or without lithium treatment and identified other potential pathways/mechanisms by which lithium can rescue Abeta pathology. Currently, we are trying to investigate/confirm one ore more of these pathways/mechanisms to identify potentially how best to rescue Abeta pathology with minimal adverse effects. We are making use of lifespan analyses and negative geotaxis assays for our rescue assays after manipulating the potential pathways.

Results
Preliminary results suggest that the manipulation of our biological pathway of interest ameliorates the Abeta pathology.

Conclusions
Lithium treatment in Abeta expressing flies, uncovered a potential biological pathway that could be important in the treatment of Abeta pathology.

Citation

Adesakin, O. A., Kerr, F., & Partridge, L. (2015, July). P1‐034: A role for lithium in rescuing amyloid beta pathology in an inducible drosophila model of Alzheimer's disease. Presented at Alzheimer's Association International Conference, Washington, D.C., USA

• Presentation Conference Type: Conference Abstract
• Conference Name: Alzheimer's Association International Conference
• Start Date: Jul 18, 2015
• Publication Date: 2015-07
• Deposit Date: May 2, 2024
• Journal: Alzheimer's & Dementia
• Print ISSN: 1552-5260
• Electronic ISSN: 1552-5279
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 7S_Part_7
• DOI: https://doi.org/10.1016/j.jalz.2015.06.230
• Public URL: http://researchrepository.napier.ac.uk/Output/3632887