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About Our Speaker
Dr. Alfred Fonteh is an Associate Professor of Neuroscience and Head of the Biomarker and Neuro-disease Mechanism Lab (BNML) in the Department of Neurosciences at HMRI. His research focuses on lipid and protein biomarkers that predict the development of Alzheimer’s disease (AD) in an otherwise cognitively healthy population. The overall objective for early AD detection is to design interventions to prevent disease progression. Since the brain loses a third of its mass in AD and lipids are a significant component of the brain, the BNML aims to detect early changes in urine or blood lipids that isolate participants who will develop AD from those who do not. Dr. Fonteh’s research also examines the proteins that change lipids to understand the underlying mechanisms for AD progression. In addition to AD, the BNML characterizes lipid disorders in migraine.
The BNML also provides analytical support for the other neuroscience labs for measuring enzyme activities, peptides, sodium and other cation changes, and cerebrospinal fluid amyloid/tau measures for the fluid biomarker classification of AD participants in the ongoing HMRI aging cohort. Finally, Dr. Fonteh’s lab prepares cerebrospinal fluid, plasma, urine, and blood cells and archives these biospecimens as part of the HMRI Aging Biorepository, comprising over 20,000 samples collected in the past 20 years.
Dr. Fonteh earned his BS in biochemistry with chemistry from Queen Mary
College, University of London, and his MS in medicinal chemistry from the Loughborough University of Technology. He completed his PhD in biochemistry at the Faculty of Medicine (School of Pharmacy) of the University of London. His research focuses on the interactions of drugs with membrane lipids, receptors, and enzymes. His interest in lipid signaling pathways led him to pursue postdoctoral studies at the Johns Hopkins University Asthma and Allergy Center, Baltimore, Maryland. His desire to use state-of-the-art technology to characterize lipids critical to human diseases enabled him to work at Wake Forest University School of Medicine in Winston-Salem, North Carolina, initially as a Research Associate, then as an Instructor of Internal Medicine, and subsequently as an Assistant Professor (1997-2001). Dr. Fonteh joined HMRI in 2001 and has served as a Senior Principal Biochemist, Research Director, and Associate Professor of Neurosciences. Several foundations and the NIH have supported his work, and he has been a major contributor to program projects and multiple RO1 grants.
Amyloid and changes in tau variants in the cerebrospinal fluid (CSF) and blood precede the clinical symptoms of AD by decades. However, treatments targeting these fluid biomarkers have not yielded clinical success. These negative outcomes suggest that scientists must look beyond amyloid/tau to prevent or treat AD. Dr. Fonteh’s approach is to examine lipid changes that will yield diagnostic profiles and disease mechanisms and thus can be targeted through lifestyle modifications or specific enzyme inhibitors. Lipids provide structural and functional roles in the brain, and oxidative stress or inflammation generates signaling lipids that disrupt neuronal function. Dr. Fonteh’s previous studies showed a lipid disorder in the CSF of AD participants, and the current practice uses CSF amyloid/tau or brain amyloid PET for AD classification. However, these methods are invasive or very expensive. Dr. Fonteh’s approach examines biomarkers in urine and blood as less invasive substitutes that can be widely applied to an aging population. Dr. Fonteh collaborates with the neurosciences clinical team at HMRI and colleagues at USC and Caltech. The BNML uses state-of-the-art mass spectrometry, ion chromatography, liquid and gas chromatography, high-sensitivity chemiluminescence detection of biomarkers, and high-performance thin-layered chromatography to isolate and quantify AD biomarkers. Dr. Fonteh’s group has discovered urine biomarkers that differentiate cognitively healthy senior participants into healthy and preclinical AD subgroups using these multivariate platforms. This discovery is significant since the urine test is non-invasive and can be applied to a general population for epidemiological and clinical studies.
Another focus of Dr. Fonteh’s lab is lipid metabolic dysfunction in migraines. Migraine is one of the leading causes of disability worldwide and is associated with psychiatric, cardiovascular, gastrointestinal, and allergic comorbidities. However, a common link between migraines and all these comorbidities is unknown. Dr. Fonteh proposes that lipids that play a role in energy regulation, vascular function, inflammation, and pain signaling are altered in migraine, and these lipid changes are the common link with its comorbidities. Dr. Fonteh collaborates with Dr. Cowan’s group at Stanford and has published several papers linking lipid metabolism to migraine pathology.
Dr. Fonteh's key contributions to science include metabolic changes in Alzheimer's disease, energy and oxidative biomarkers in Alzheimer's disease diagnosis, and migraine research.
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