Description
Genetic studies in Alzheimer’s disease (AD) strongly suggest that lipoprotein metabolism is one of the major pathways in the pathogenesis of AD. Currently, several gene variants or isoforms (e.g., apoE, apoJ, clusterin, ABCA7, SORL1, PICALM, and BIN1) that are related to lipid metabolism, transport, trafficking, and endocytosis have been associated with increased risk for AD. However, the underlying mechanism(s) and what exact roles lipids play in the development of AD are poorly understood.
The study of lipid metabolic pathways in the central nervous system (CNS) has been largely neglected to date. However, understanding how lipid/lipoprotein metabolism in the brain and body affect cognitive function is essential for establishing the mechanistic basis on which effective therapeutics and novel diagnostics for AD can be developed. Thus, coordinated efforts to combine expertise in neurobiology and lipid biology, which is readily available at different institutes at the NIH, are paramount to achieving the goals that have been set as a national priority for the prevention and effective treatment of AD and other neurodegenerative diseases.
Traditionally, investigators with the most experience in lipid and lipoprotein metabolism are funded by NHLBI, while investigators studying neurodegeneration are usually funded by the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS). Thus, very few NHLBI-funded investigators with strong expertise in lipid metabolism are able to cross the field to study lipid metabolism in CNS and examine the roles of lipids in the pathogenesis of AD and AD-related dementias, and vice versa. The goal of the working group was to bring together experts from both areas of lipid and lipoprotein metabolism and neurodegeneration to examine the current state of the science relating lipid and lipoprotein metabolism and AD, to identify gaps and barriers that would need to be removed to help move the field forward, and to recommend future research opportunities for NHLBI in lipid and lipoprotein metabolism and AD.
Discussions
Presentations and discussions focused on the following themes:
- ApoE and ApoE receptors in the CNS and beyond, and their relations to neurodegenerative and vascular diseases
- Neuronal cell biology and lipid trafficking and transport
- Neurovascular mechanisms and neurodegeneration
- Neuronal lipid metabolism, lipid signaling, and inflammation
- Alzheimer’s disease-related dementia research in NHLBI cohort studies
Several under-researched areas were identified, including the role of the blood-brain barrier (BBB), neurovascular and neurosynaptic mechanisms, and lipid biology of the CNS in the pathogenesis of human dementia and AD.
NHLBI Contacts:
Lijuan Liu, Ph.D.
NIH/NHLBI/DCVS/ACAD
Phone: 301-435-0582
Email: lliu@mail.nih.gov
Michelle Olive, Ph.D.
NIH/NHLBI/DCVS/ACAD
Phone: 301-435-0550
Email: olivem@mail.nih.gov
Working Group Participants:
Chair: Joachim Herz, M.D., UT Southwestern Medical Center
Speakers:
- Shawn Ferguson, Ph.D., Yale University
- Christopher Glass, M.D., Ph.D., University of California, San Diego
- David Holtzman, M.D., Washington University
- Costantino Iadecola, M.D., Cornell University
- Alan Remaley, M.D., Ph.D., NHLBI
- Tarek Samad, Ph.D., Pfizer Worldwide Research and Development
- Peter Tontonoz, M.D., Ph.D., University of California, Los Angeles
- Cheryl Wellington, Ph.D., The University of British Columbia
- Jacqueline Wright, Dr.P.H., NHLBI
- Berislav Zlokovic, M.D., Ph.D., University of Southern California
Participants from NHLBI and other NIH Institutes:
- Yves Rosenberg, M.D., NHLBI
- Zorina Galis, Ph.D., NHLBI
- Suzana Petanceska, Ph.D., NIA
- Luke Stoeckel, Ph.D. NIDDK
- Francesca Bosetti, Pharm.D., Ph.D., NINDS
- Michael Ward, M.D., Ph.D., NINDS