Mary Konsolaki
Associate Research Professor

Analysis of toxicity associated with Alzheimer's beta-amyloid. using Drosophila as a model system

My research interests focus on understanding Alzheimer's disease (AD). a neurological disorder resulting in the degeneration and eventual death of neurons in brain centers controlling memory. cognition and behavior. Human genetic analyses have resulted in the identification of a handful of genes responsible for genetically inherited forms of Alzheimer's disease but our understanding of basic mechanisms that lead to the more common sporadic forms of this disease is still limited.

Overproduction of beta-amyloid (Ab) peptides in the brain is widely believed to be a causative event in the disease process. Research work in my lab has concentrated on trying to better understand the molecular pathways associated with production as well as toxicity and clearance of Ab peptides. using Drosophila as a model system.

We have shown that flies expressing Ab peptides can closely mimic phenotypic. behavioral and physiological aspects of Alzheimer's disease. Ab peptides accumulate in a dose- and age dependent manner in flies. causing phenotypes that are associated with neurodegeneration. such as locomotion defects and shorter lifespan. We are currently using these flies in genetic screens to identify genes involved in Ab metabolism and toxicity. In order to understand the functions of such genes. a variety of approaches is used. including genetics as well as behavioral. molecular. biochemical and cell-biological methods.

Selected Publications

van de Hoef DL, Hughes J, Livne-Bar I, Garza D, Konsolaki M, Boulianne GL. (2009)
Identifying genes that interact with Drosophila presenilin and amyloid precursor protein.
Genesis. 47(4):246-60.

Tan L, Schedl P, Song HJ, Garza D, Konsolaki M. (2008) The Toll-->NFkappaB signaling pathway mediates the neuropathological effects of the human Alzheimer's Abeta42 polypeptide in Drosophila. PLoS ONE. 3(12):e3966.

Cao W, Song HJ, Gangi T, Kelkar A, Antani I, Garza D, Konsolaki M. (2008) Identification of novel genes that modify phenotypes induced by Alzheimer's beta-amyloid overexpression in Drosophila. Genetics. 178(3):1457-71.

Finelli A, Kelkar A, Song HJ, Yang H, Konsolaki M. (2004) A model for studying Alzheimer's Abeta42-induced toxicity in Drosophila melanogaster. Mol Cell Neurosci. 26(3):365-75.

Iijima. K.. Liu. H-P.. Chiang. A-S.. Hearn. S.A.. Konsolaki. M. and Zhong. Y. (2004). Dissecting the pathological effects of human A 40 and A 42 in Drosophila: A potential model for Alzheimer's disease. Proc. Natl. Acad. Sci. USA 101:6623-6628.

Konsolaki. M. and Cohen. D. (2004). Targets for Alzheimers: lessons learnt from flies. DDT: TARGETS 3:64-70.