LaDu Lab Mission:
1. INVESTIGATE: the interaction of apoE and Aβ as modulated by universal biological variables for AD (age, APOE, and sex).
2. INNOVATE: predictive biomarkers and novel preclinical drug trials based on the universal biological variables.
3. EDUCATE: inspire the next generation of exceptional scientists and physicians.
Alzheimer's disease (AD) is a fatal neurodegenerative disease diagnosed post-mortem by the presence of amyloid plaques and neurofibrillary tangles. Familial AD (early onset ≤ age 65), caused by the overexpression of amyloid-β peptide (Aβ), affects 0.2 million people in the U.S., however, sporadic AD (late onset ≥ age 65) affects 5.6 million people.
While age is the greatest overall risk factor for sporadic AD, the APOE4 gene, encoding the apolipoprotein E4 (apoE4) isoform, is the greatest genetic risk factor for AD, increasing risk up to 15 fold compared to the common APOE3 genotype. APOE4 is associated with increased levels of Aβ, resulting in increased levels of both amyloid plaques and soluble neurotoxic oligomeric Aβ (oAβ). Importantly, female APOE4 carriers have a greater lifetime risk for developing AD, an increased rate of cognitive decline, and an accelerated accumulation of Aβ compared to male APOE4 carriers. Those three risk factors, age, APOE genotype, and sex, are together classified as the universal biological variables for AD.
Our lab focuses on the properties and interactions between the two proteins that are linked to AD: Aβ and apoE, in the context of the universal biological variables. Our research on AD is conducted using the novel EFAD transgenic mouse model that expresses human APOE and develops AD-like pathology, which allows for stratification by APOE genotype and sex. Thus, the EFAD mice allow us to assess how the interaction between APOE and Aβ is influenced by the universal biological variables.
Lewandowski, C.T., Khanb, Md.W., BenAissa, M., Dubrovskyi, O., Ackerman-Berrier, M., LaDu, M.J., Layden, B.T., and Thatcher, G.R.J.
Metabolomic analysis of a selective ABCA1 inducer in obesogenic challenge provides a rationale for therapeutic development.
EBioMedicine. 2021 Mar. doi: 10.1016/j.ebiom.2021.103287.
Tai, L.M., Maldonado Weng, J., LaDu, M.J., and Brady, S.T.
Relavence of transgenic mouse models for Alzheimer's disease.
Progress in Molecular Biology and Translational Science. 2020 Aug. doi: 10.1016/bs.pmbts.2020.07.007.
Lewandowski, C.T., Maldonado Weng, J., and M.J. LaDu.
Alzheimer's disease pathology in ApoE transgenic mouse models: The Who, What, When, Where, Why, and How.
Neurobiology of Disease. 2020 Feb.
The LaDu lab is funded by NIH (NIA) R01 AG056472, R01 AG057008, UH2/3 NS10012, R56 AG058655, 1R44 AG060826, AD Assoc. SAGA, UIC-DPI Phase 2 POC Award, pharmaceutical company contracts and philanthropic support from Lou and Christine Friedrich.