Biomarker and Neuro-disease Mechanism Laboratory (BNML), a lab within Huntington Medical Research Institutes (HMRI) Clinical and TranslationalNeurosciences led by Alfred N. Fonteh, PhD, focuses on the detection, quantification, and associations of markers and mechanisms in Alzheimer’s pathology and symptoms.
Alzheimer’s Disease Mechanisms
BNML researchers are examining short-chain and medium-chain plasma lipids as markers for different stages of development in Alzheimer’s pathology and symptoms. They also collaborate with the University of Southern California (USC) to examine urine lipid metabolites in association with AD and related dementias.
BNML researchers are also testing the hypothesis that differences in lipid metabolism can reveal mechanisms of AD that can be targeted for treatment. Lab members use sensitive mass spectrometry instruments to quantify metabolic components of CSF, plasma, and urine in order to discover differences that may account for different stages of AD pathogenesis
Novel Alzheimer’s Disease Therapies
BNML researchers are investigating prevention of AD pathogenesis via use of anti-inflammatory agents, anti-oxidants, and supplementation with energy-generating compounds and substrates that maintain the structure and function of a healthy brain.?
Dysfunctional Lipid Pathways in Migraine
BNML researchers have also collaborated with Stanford University researchers to find that aspects of lipid metabolism can be targeted for novel migraine drugs?.
Key findings
- Identified Phospholipase A2 and PC-Phospholipase C isoforms that change in migraine and examined activity inhibitors as potential migraine drugs?.
- Lipolysis pathways and migraine – Measured plasma-free fatty acids in control and migraine participants. Measured plasma metabolic hormones (insulin, glucagon, ghrelin, leptin) and stress hormones?.
- There are changes in neuromodulator levels (Magnesium, and neurotransmitters) levels or metabolism in migraine.?
- Changes in plasma lipids are significantly associated with brain regions (Voxel MRI) and connectivity networks (fMRI) associated with pain processing.
-
Chew, H., Victoria A. Solomon, V.A., A.N. Fonteh, Involvement of
lipids in Alzheimer’s diseases pathology and potential therapies. Front. Physiol. Lipid and Fatty Acid Research Volume 11 2020.
- Fonteh, A.N , Cipolla, M., Chiang, J., Arakaki, X., MG. Harrington., Human Cerebrospinal Fluid Fatty Acid Levels Differ between Supernatant Fluid and Brain-Derived Nanoparticle Fractions,
and Are Altered in Alzheimer's Disease. Published: June 23, 2014.
- Fonteh, A.N., Harrington, R., Tsai, A. et al. Free amino acid and dipeptide changes in the body fluids from Alzheimer’s disease subjects. Amino Acids 32, 213–224 (2007).
The Biomarkers Neuro-Disease Mechanism Lab (BNML) is led by Alfred Fonteh, PhD, who has investigated biomarkers and mechanisms of Alzheimer’s disease for 21 years. Alzheimer’s disease (AD) is the most common form of dementia and the seventh leading cause of death in the United States. According to recent statistics from the Alzheimer’s Association, 6.7 million people aged 60 or older are living with Alzheimer’s disease in the United States. Dr. Fonteh was inspired by family members and friends who have suffered from AD without any medical help and is dedicated to discovering potential biomarkers for Alzheimer’s disease in the early stages of pathology. Dr. Fonteh is also interested in investigating AD causes for pharmacologic and non-pharmacologic therapies, or preventive options.
There is an incipient and silent (preclinical) stage of Alzheimer’s disease before the emergence of cognitive symptoms of either Mild Cognitive Impairment (MCI) or dementia. More research is needed to understand if this preclinical stage is a valid representation of people who may go on to develop Alzheimer’s disease. Dr. Fonteh’s lab is well-focused on the establishment of a conclusive connection between biomarkers and the preclinical stage of Alzheimer’s disease.?With advancements in early detection, there is potential for patients to learn about their risk for AD before clinical symptoms appear and receive early treatment.
Dr. Fonteh has mentored numerous young scientists with similar research interests over the course of his career. One of his current mentees is Joby Jose, PhD, a postdoctoral fellow in the BNML lab who focuses on experiments for biomarkers. Together, Dr. Fonteh and Dr. Jose work closely with the Clinical Brain Aging Group and the Analytical Biochemistry Core (ABC), which manage clinical recruitment and classification and maintain sophisticated laboratory equipment, respectively.
The primary focus of research in BNML is on non-invasive biomarkers that enable the widespread screening and early diagnosis of Alzheimer’s disease. The laboratory has successfully studied the correlation between energy-related and oxidatively derived short-chain and medium-chain lipids in cognitively healthy (CH), Mild Cognitive Impairment (MCI), and Alzheimer’s disease (AD) subjects. We are currently investigating the fluctuations of brain-derived lipids in subjects at various stages of Alzheimer’s disease. Other significant studies in our laboratory include the correlation between bioenergetics and mitochondrial dysfunction and disturbances in the neuromodulator pathways associated with Alzheimer’s disease.
Joby Jose, PhD is originally from Thodupuzha, Kerala, India. He received his PhD in Biochemistry from Kannur University in India, where he studied the anti-carcinogenic properties of selected flavonoids and their bioavailability and biodegradation. Dr. Jose joined HMRI in February of 2023 as a Postdoctoral Fellow in the Biomarker and Neuro-disease Mechanism Lab (BNML), where he researches and identifies novel biomarkers for Alzheimer’s disease in early disease conditions.
My Why: “Alzheimer’s disease (AD) is the most common form of dementia and the sixth leading cause of death in the US. Currently, there is no cure, detection methods are limited to select patients, and they lack potential biomarkers to predict the onset of the disease. Current diagnostic techniques are not widely available or applicable to many patients due to the invasiveness of CSF collection and PET imaging and the high expenses for these procedures. So, there is an urgent requirement for a cheaper, non-invasive biomarker. My research focuses primarily on the identification of novel biomarkers to predict the onset of Alzheimer’s disease in cognitively healthy individuals.”
Fun Fact: Dr. Jose’s favorite thing is traveling. “It helps me find myself and gain a better perspective of myself.” He also has a passion for tasting unique foods from around the world.
Alfred N. Fonteh, PhD
Associate Professor, Clinical and Translational Neurosciences
The Biomarkers Neuro-Disease Mechanism Lab (BNML) is led by Alfred Fonteh, PhD, who has investigated biomarkers and mechanisms of Alzheimer’s disease for 21 years. Alzheimer’s disease (AD) is the most common form of dementia and the seventh leading cause of death in the United States. According to recent statistics from the Alzheimer’s Association, 6.7 million people aged 60 or older are living with Alzheimer’s disease in the United States. Dr. Fonteh was inspired by family members and friends who have suffered from AD without any medical help and is dedicated to discovering potential biomarkers for Alzheimer’s disease in the early stages of pathology. Dr. Fonteh is also interested in investigating AD causes for pharmacologic and non-pharmacologic therapies, or preventive options.
There is an incipient and silent (preclinical) stage of Alzheimer’s disease before the emergence of cognitive symptoms of either Mild Cognitive Impairment (MCI) or dementia. More research is needed to understand if this preclinical stage is a valid representation of people who may go on to develop Alzheimer’s disease. Dr. Fonteh’s lab is well-focused on the establishment of a conclusive connection between biomarkers and the preclinical stage of Alzheimer’s disease.?With advancements in early detection, there is potential for patients to learn about their risk for AD before clinical symptoms appear and receive early treatment.
Dr. Fonteh has mentored numerous young scientists with similar research interests over the course of his career. One of his current mentees is Joby Jose, PhD, a postdoctoral fellow in the BNML lab who focuses on experiments for biomarkers. Together, Dr. Fonteh and Dr. Jose work closely with the Clinical Brain Aging Group and the Analytical Biochemistry Core (ABC), which manage clinical recruitment and classification and maintain sophisticated laboratory equipment, respectively.
The primary focus of research in BNML is on non-invasive biomarkers that enable the widespread screening and early diagnosis of Alzheimer’s disease. The laboratory has successfully studied the correlation between energy-related and oxidatively derived short-chain and medium-chain lipids in cognitively healthy (CH), Mild Cognitive Impairment (MCI), and Alzheimer’s disease (AD) subjects. We are currently investigating the fluctuations of brain-derived lipids in subjects at various stages of Alzheimer’s disease. Other significant studies in our laboratory include the correlation between bioenergetics and mitochondrial dysfunction and disturbances in the neuromodulator pathways associated with Alzheimer’s disease.
Joby Jose, PhD
Postdoctoral Research Scholar
Clinical and Translational Neurosciences
Joby Jose, PhD is originally from Thodupuzha, Kerala, India. He received his PhD in Biochemistry from Kannur University in India, where he studied the anti-carcinogenic properties of selected flavonoids and their bioavailability and biodegradation. Dr. Jose joined HMRI in February of 2023 as a Postdoctoral Fellow in the Biomarker and Neuro-disease Mechanism Lab (BNML), where he researches and identifies novel biomarkers for Alzheimer’s disease in early disease conditions.
My Why: “Alzheimer’s disease (AD) is the most common form of dementia and the sixth leading cause of death in the US. Currently, there is no cure, detection methods are limited to select patients, and they lack potential biomarkers to predict the onset of the disease. Current diagnostic techniques are not widely available or applicable to many patients due to the invasiveness of CSF collection and PET imaging and the high expenses for these procedures. So, there is an urgent requirement for a cheaper, non-invasive biomarker. My research focuses primarily on the identification of novel biomarkers to predict the onset of Alzheimer’s disease in cognitively healthy individuals.”
Fun Fact: Dr. Jose’s favorite thing is traveling. “It helps me find myself and gain a better perspective of myself.” He also has a passion for tasting unique foods from around the world.
