Mary Jo LaDu
Professor, Department of Anatomy & Cell Biology, College of Medicine
Office: 7091 COMRB
Lab: 7060 COMRB
Phone: 312 355-4795
Web Site: Mary Jo LaDu Laboratory Page
The goal of our lab is to identify targets that mediate APOE– and sex-specific effects on the risk and pathology of Alzheimer’s disease (AD) to inform both therapeutic strategies and biomarker development. Our lab studies lipoprotein biogenesis in the brain where the only apolipoprotein expressed is apolipoprotein E (apoE). A naturally occurring genotype of APOE, APOE4, increases the risk for AD 4- and 12-fold over the more common APOE3 genotype. Importantly, this risk increases significantly in APOE4 females. APOE4 is associated with the accelerated accumulation of the amyloid-b (Ab) peptide, which aggregates to form both amyloid plaques and soluble oligomeric Ab (oAb), likely the proximal neurotoxin. Our data demonstrate that established differences between APOE4 vs. APOE3 are mimicked by female vs. male, differences that include Ab aggregation/accumulation and apoE levels/lipidation. Thus, our work focuses on therapeutic approaches to correct apoE4 structure and function in the EFAD transgenic mice, a unique transgenic mouse model created by our lab that expresses familial AD mutations and the human APOE genotypes. In collaboration with industry partners, we are currently testing several therapeutics in the EFAD mice, drugs that target apoE lipidation, estrogen alternatives, and neuroinflammation. As well, we are working on a novel biomarker for AD that can be measured in the blood
Tai LM, Balu D, Avila-Munoz E, Abdullah L, Thomas R, Collins N, Valencia-Olvera AC, and M.J. LaDu. EFAD Transgenic Mice as a Human APOE Relevant Preclinical Model of Alzheimer’s Disease. Journal Lipid Research. 2017 April 7. pii: jlr.R076315. doi: 10.1194/jlr.R076315. PMID: 28389477.
Ghura, S., Tai, L.M., Zhao, M., Collins, N.C., Che, C-T., and K.M. Warpeha, K.M., and M.J. LaDu. Arabidopsis thaliana extracts optimized for polyphenols production as potential therapeutics for the APOE-modulated neuroinflammation characteristic of Alzheimer’s disease in vitro. Scientific Reports. 2016. 6, 29364; doi: 10.1038/srep29364. PMID: 27383500. PMCID: 4935988.
Tai, L., Ghura, S., Koster, K., Liakaite, V., Maienschein-Cline, M., Kanabar, P., Collins, N., Ben-Aissa, M., Zhengdeng Lei, A., Bahroos, N., Green. S., Hendrickson, W., Van Eldik. L.J., and M.J. LaDu. APOE modulated Ab-induced neuroinflammation in Alzheimer’s disease: current landscape, novel data and future perspective. Invited review Journal of Neurochemistry. 2015 May 13. doi: 10.1111/jnc.13072. PMID: 25689586. PMCID: PMC4400246.
Tai, L.M., Koster, K.P., Luo, J., Lee, S.H., Wang, Y-T, Collins, N.C., Ben Aissa, M., Thatcher, G.R.J., and M.J. LaDu. Amyloid-b pathology and APOE genotype modulate retinoid x receptor agonist activity in vivo. Journal of Biological Chemistry, doi: 10.1074/jbc.M114.600833. 2014. PMID: 25217640. PMCID: PMC4215234
Youmans, K.L., Tai, L.M., Nwabuisi-Heath, E., Jungbauer, L.M., Kanekiyo, T., Gan, M., Kim, W., Eimer, W.A., Estus, S., Rebeck, G.W., Weeber, E., Bu, G., Yu, C., and M.J. LaDu. APOE4-specific changes in Ab accumulation in a new transgenic mouse model of Alzheimer’s disease. Journal of Biological Chemistry, 287(50):41774-86, 2012. PMID: 23060451. PMCID: PMC3516726.