Mary Jo LaDu

LaDuPhD, University of Illinois

Professor, Department of Anatomy & Cell Biology, College of Medicine

Office: 7091 COMRB

Lab: 7060 COMRB

Phone: 312 355-4795

email: mladu@uic.edu

Web Site: Mary Jo LaDu Laboratory Page

 

Research Interests:

Dr. LaDu’s lab studies the pathology of Alzheimer disease (AD) by focusing on the structure/function interactions between the human isoforms of apolipoprotein E (apoE) and amyloid-β peptide (Aβ). A naturally occurring isoform of the APOE gene, apoE4, increases lifetime risk for AD 60-fold compared to the more common apoE3. Aβ, particularly oligomeric aggregates (oAβ), is considered a major cause of AD. Importantly, among APOE4 carriers, females have a greater lifetime risk for developing AD, an increased rate of cognitive decline and accelerated accumulation of Aβ compared to males. Our overall hypothesis is that apoE4 and oAβ act synergistically to compromise neuronal viability. Our mechanistic hypothesis is that aging, APOE4, female sex, and AD pathology interact to reduce apoE lipidation, impairing clearance of soluble Aβ, resulting in synaptic loss, memory/cognitive deficits, and dementia. We utilize an integrated approach to address the complexity of apoE/Aβ interactions, including biochemical, molecular biology, and cell biology methods using in vitro, ex vivo, and in vivo models. Our goal is to develop oAβ and apoE/Aβ complex as “mechanistic biomarkers” and therapeutic targets as both are significant prior to neuronal damage.

 

Publications:

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., & LaDu, M.J. APOE modulated Aβ-induced neuroinflammation in Alzheimer’s disease: current landscape, novel data and future perspective. J. Neurochem., 133 (2015) 465-488. (PMID: 25689586)

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 LaDu, M.J.. Amyloid-β pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo. J. Biol. Chem., 289 (2014) 30538-30555. (PMID: 25217640)

Tai, L.M., Bilousova, T., Jungbauer, L., Roeske, S.K., Yu, C., Estus, S., Bu, G., Van Eldik, L., Gylys, K., and LaDu, M.J.. Soluble apolipoprotein E/amyloid-β (apoE/Aβ) complex levels are reduced in Alzheimer’s disease patients and further with APOE4 in AD transgenic mice and human samples. J. Biol. Chem., 288 5914-5926. (PMID: 23293020)

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., & LaDu, M.J. APOE4-specific changes in Abeta accumulation in a new transgenic mouse model of Alzheimer’s disease. J. Biol. Chem., 287 (2012) 41774-41786. (PMID: 23060451)

Youmans, K., Tai, L.M., Kanekiyo, T., Stine, W.B., Michon S.C., Nwabuisi-Heath, E., Manelli, A.M., Fu, Y., Riordan, S., Eimer, W.A., Binder, L., Bu, G., Hartley, D.M., &  LaDu, M.J. Intraneuronal Abeta detection in 5xFAD mice by a new Aβ-specific antibody. Mol. Neurodegen., 7 (2012) 8. (PMID: 22423893)