Ling Li

ling liAlzheimer’s Disease Research

Professor and VFW Endowed Chair in Pharmacotherapy for the Elderly Ling Li is an expert in Alzheimer’s disease and atherosclerosis, age-related disorders leading to memory loss and heart attack, respectively. Her research focuses on cholesterol and related molecules and their impact on brain function as well as cardiovascular disease.

“The high-density lipoprotein (HDL), commonly known as the ‘good’ cholesterol, has been established as a protective factor for heart disease and our hypothesis is that what’s good for the heart is also good for the brain”

“HDL is a modifiable factor by lifestyle and also by application of drugs,” said Li.

One of Li’s ongoing research projects is focused on improving vascular function with HDL and its implications for brain function, including cognition. Her previous research focused on the role of statins, drugs that lower the “bad” low-density lipoproteins (LDL) cholesterol, in lowering the risk of Alzheimer’s disease.

“For public health age-related conditions, it is still much more important to find preventive approaches or strategies,” said Li. “Lifestyle changes, including diet and exercise, are both effective in terms of improving HDL function.”

She has also taken Alzheimer’s disease research in a new direction. In the early 1990s, the connection between cardiovascular disease and the brain was established. Genetically, the inheritance of the APOE4 gene, which is associated with an increased risk of cardiovascular disease, was identified to be the preeminent genetic risk factor for Alzheimer’s disease. 

Although the mechanisms by which APOE4 influences the development of AD are not completely understood, compelling evidence indicates that the pathogenic effects of APOE4 are mediated through lipid-related pathways. Compared with the more common APOE3 isoform, APOE4 exhibits a deficiency in lipidation and formation of HDL in the brain.

Li’s recent research shows that HDL mimetic peptides may be capable of reversing APOE4 lipidation and functional deficits and mitigating the toxic effects of amyloid-beta protein, a widely recognized culprit of Alzheimer’s disease. Thus it could potentially slow and prevent memory loss associated with Alzheimer’s disease.

“The good news is that these HDL-mimetic peptides have been proven to be vascular protective in animal models and some have advanced into human clinical trials for cardiovascular disease,” said Li. “We are repurposing these promising vascular protective and anti-inflammatory peptides to preventing the toxic amyloid-beta protein from building up in the brain. Our research has focused on tackling Alzheimer’s by improving both cardiovascular and brain health.”

According to Li, one magic bullet will most likely not solve this chronic disease.

“Alzheimer’s disease is a multi-factorial disease,” said Li. “Multiple factors contribute to the development of the disease and we will need a combination of approaches to prevent, delay or treat this societal problem. It’s imperative that we find novel therapeutic strategies using dietary, genetic and pharmacological approaches to combat this devastating disease.”