Alzheimer disease (AD) has reached epidemic proportions, representing a serious economic and social burden worldwide.

• Over the last decade, AD mortality has increased 66% to become the sixth leading cause of death.
• AD occurs in 1 of 8 Americans aged 65 and 50% over age 85.
• The current annual cost to America is ~$183 billion, increasing to 1.1 trillion by 2050.
• Currently there is no cure and only temporary symptomatic management is available.

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. Our overall hypothesis is that apoE4 and oAβ act synergistically to compromise neuronal viability. 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.

Neuron stained via novel method to identify earliest possible markers for neuronal distress. Heath, JNS, 2012

Current research interests include:
• Effect of APOE genotype on Aβ accumulation and speciation
• Role of apoE/Aβ complex in Aβ clearance with a focus on ApoE isoform, apoE levels and apoE lipidation.
• oAβ and apoE/Aβ ELISAs as mechanistic biomarkers for AD progression.
• Effect of apoE isoform on inflammation and synapse viability.
• Development and testing of AD therapeutics including:
  • ApoE-dependent therapeutics targeting apoE/Aβ complex and neuroinflammation.
  • ApoE-independent therapeutics whose efficacy may be affected by apoE