My research involves working towards an understanding of the mechanisms underlying diseases causing dementia, as well as clinical trials that impact these disorders. In addition to clinical trials, I direct the Dementia Brain, Blood and Cerebrospinal Fluid Bank. My research laboratory and its staff support basic and translational research involving AD patients, and patients with other degenerative diseases impacting cognition.
- Carol F. Lippa, M.D.
Professor and Interim Chair; Director, Division of Cognitive Disorders and Memory Disorder Center
Carol F. Lippa, M.D. | Yue-Song Gong, Ph.D.
The clinical component of the program focuses on the management of patients with dementia and degenerative diseases. Working closely with our neuropsychologists and psychiatrists, we focus upon behavioral and pharmacological management of the behavioral manifestations of these disorders. The Division of Dementia and Memory Disorders encompasses research, patient evaluation and education about Alzheimer's disease (AD) and other forms of dementia. Our overall goals include:
- Working towards an understanding of the mechanisms underlying diseases causing dementia.
- Providing medical management to people with Alzheimer's disease and other types of dementia until an effective means to prevent or treat these diseases becomes available.
- Educating residents, medical students, patients and their families about these diseases.
The Division of Dementia and Memory Disorders was established in 1996 by Carol F. Lippa, M.D., a neurologist with extensive experience diagnosing and managing patients with disorders of memory and thinking. Dr. Lippa has dedicated her outpatient practice to the evaluation and management of Alzheimer's disease, age-related memory loss, Pick's and Lewy body dementias and related disorders. Currently the chief of the Division of Dementia and Memory Disorders, Dr. Lippa and her associates are responsible for the education of residents and medical students in this area.
Dr. Lippa and her associates maintain two laboratories within the Drexel University system. Dr. Lippa directs the Dementia and Degenerative Disease Brain, Blood and Cerebrospinal Fluid Bank at Drexel. Here she maintains her NIA-funded laboratory and staff to support basic research involving the study of abnormal proteins that accumulate in the brains of Alzheimer's patients, and patients with other degenerative diseases. Medical students and neurology residents with an interest in developing research skills in this area are active in this laboratory.
Alzheimer's Disease Research
The hallmark pathological lesions of Alzheimer's disease are β-amyloid (Aβ) plaques, neurofibrillary tangles, and synaptic loss. Among these, Aβ plaques and tangles can be detected decades before symptoms arise. Synaptic loss begins in preclinical Alzheimer's disease and is the strongest anatomical correlate of the degree of clinical impairment in the disease. The molecular pathophysiology of synaptic dysfunction remains elusive, particularly the molecular events that occur at the synapse. Recently, the accumulation of evidence demonstrates the level of soluble amyloid is related to synaptic loss in Alzheimer's disease. The soluble amyloid from a human Alzheimer's brain shows specific pathological characterization that is different from the artificial soluble amyloid.
In the laboratory of Yue-Song Gong, Ph.D., we are working on:
- Identifying the pathogenic template of natural soluble assemblies of β-amyloid in human Alzheimer's disease, which may play a transmissible role in the disruption of the synapse.
- Using native pathogenic oligomers of Aβ and phosphorylated Tau as a vaccine or to develop a specific antibody to clean the toxic proteins in preclinical Alzheimer's disease.
- Exploring the pathological roles of aging-relevant insulin receptor-mTOR signal pathway in the disruption of synaptic protein network in preclinical Alzheimer's disease.
- Developing effective therapeutics such as to screen natural compounds and novel synthesized compounds to regulate insulin receptor-mTOR and NMDA receptor-relevant synaptic protection signal pathways to improve synaptic function and prevent synaptic loss in preclinical Alzheimer's disease.
- Identifying the common pathogenic mechanism of oligomerization among natural oligomers including Aβ , tau, prion protein (PrP), α-synuclein and huntingtin, underlying synaptic dysfunction in neurodegenerative diseases.
Scientific methods used include:
- Proteomics analysis to identify the pathological changes in the synapse of Alzheimer's patient brains.
- Western blot to confirm the pathological protein network in the synapse of human Alzheimer's brains.
- Immunocytochemistry and confocal microscopy to observe how the cancer- and age-relevant signal pathways and NMDA receptor are involved in the regeneration and degeneration of the dendritic spine in AD development.
- Water maze to test compounds to improve the memory function of AD mice
- Traditional and modern methods to develop monoclonal antibodies to natural oligomers of Aβ.
In the future, we will screen specific and high affinity antibodies to oligomers of Aβ to clean misfolding proteins in Alzheimer's brains. We will also screen novel compounds to normalize insulin receptor and NMDA receptor activity to protect synaptic function, prevent the synaptic degeneration, and increase the synaptic formation in preclinical research. These will be tested in different Alzheimer's model animals. In addition, we will also develop more antibodies to cancer- and aging-relevant proteins to detect the pathological proteins in CSF and blood for Alzheimer's diagnosis. We will also study how to use the synaptic protein network such as Pin1, Shank proteins as novel targets to protect synaptic function in preclinical Alzheimer's disease.
Clinical Trials for Memory Disorders Patients
In addition to laboratory research, the Memory Disorders Center conducts a number of clinical trials through our clinical practice, Drexel Neurology. Learn more about participation in a memory disorders clinical trial.
If you or a loved one is showing signs of dementia or a memory problem, visit Drexel Neurology to learn how we can help.