Director

Meet the Director

Hussein Yassine, MD
Professor of Neurology, of Medicine and of Physiology and Neuroscience

Dr. Hussein Yassine, professor at the Keck School of Medicine of USC, is at the forefront of research exploring the intersection of neurology and nutritional sciences, with a focus on how lipids, particularly omega-3 fatty acids, affect Alzheimer’s disease. His work is especially important in understanding the impact of these fatty acids on cognitive decline in those carrying the APOE ε4 gene variant, a known Alzheimer’s risk factor.

Dr. Yassine’s lab conducts a broad range of research, from basic science and brain imaging to clinical trials with omega-3 supplements and dietary interventions, making significant strides in our understanding of how nutrition influences Alzheimer’s.

In addition to his research, Dr. Yassine is committed to teaching and mentoring the next generation of medical and research professionals. He advocates for lifestyle changes, such as diet and exercise, particularly in middle age, to reduce Alzheimer’s risk. This approach extends to public health, influencing understanding of, and practices in, Alzheimer’s prevention and care.

Under Dr. Yassine’s guidance, the 2023 launch of the USC Center for Personalized Brain Health marks a step forward in Alzheimer’s research. The center exemplifies a multidisciplinary approach, targeting early detection and intervention for those at elevated risk due to the APOE ε4 gene variant. This initiative reflects USC’s dedication to evolving dementia research and care. Through collaborative, comprehensive research, Dr. Hussein and his colleagues aim to reduce the public health impact of Alzheimer’s disease and strive for a future where Alzheimer’s disease is no longer a major threat to people’s health and well-being.

Visit the Yassine Lab website for more details on his research and contributions.

Selected Publications from the Yassine Lab

Can the gut microbiome inform the effects of omega-3 fatty acid supplementation trials on cognition?

January 3, 2024

PURPOSE OF REVIEW: Most omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation clinical trials report inconsistent or null findings on measures of cognition or Alzheimer’s disease (AD) with a relatively large variability in the response to n-3 PUFA supplementation. The purpose of this review is to identify whether the gut microbiome together with the metabolome can […]
Bilal E Kerman

Synthesis and Preclinical Evaluation of 22-[¹⁸F]Fluorodocosahexaenoic Acid as a Positron Emission Tomography Probe for Monitoring Brain Docosahexaenoic Acid Uptake Kinetics

December 4, 2023

Docosahexaenoic acid [22:6(n-3), DHA], a polyunsaturated fatty acid, has an important role in regulating neuronal functions and in normal brain development. Dysregulated brain DHA uptake and metabolism are found in individuals carrying the APOE ε4 allele, which increases the genetic risk for Alzheimer’s disease (AD), and are implicated in the progression of several neurodegenerative disorders. However, […]
Marlon Vincent V Duro

Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE ε4 Carriers before the Onset of Dementia

October 24, 2023

CONCLUSIONS: Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.
H N Yassine

State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer’s Disease

August 23, 2023

Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, with devastating public health consequences. While peripheral insulin resistance is a key feature of most forms of T2DM and has been investigated for over a century, research on brain insulin resistance (BIR) has more recently been developed, including in the context of T2DM […]
Elizabeth M Rhea

An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE ε4 allele

May 23, 2023

Carrying the apolipoprotein E (APOE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer’s disease, but the degree to which APOE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) APOE glycosylation profiles, with the E4 […]
Cristiana J Meuret

Associations of APOE ε4 status and DHA supplementation on plasma and CSF lipid profiles and entorhinal cortex thickness

March 23, 2023

Apolipoprotein ε allele 4 (APOE ε4) influences the metabolism of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The entorhinal cortex (EC) in the brain is affected early in Alzheimer’s disease and is rich in DHA. The purpose of this study is to identify the effect of APOE ε4 and DHA lipid species on the EC. […]
Mikaila Ann Bantugan

Nutritional metabolism and cerebral bioenergetics in Alzheimer’s disease and related dementias

December 8, 2022

Disturbances in the brain’s capacity to meet its energy demand increase the risk of synaptic loss, neurodegeneration, and cognitive decline. Nutritional and metabolic interventions that target metabolic pathways combined with diagnostics to identify deficits in cerebral bioenergetics may therefore offer novel therapeutic potential for Alzheimer’s disease (AD) prevention and management. Many diet-derived natural bioactive components […]
Hussein N Yassine

APOE ε4 and Alzheimer’s disease diagnosis associated differences in L-carnitine, GBB, TMAO, and acylcarnitines in blood and brain

November 27, 2022

BACKGROUND: The apolipoprotein E (APOE) ε4 allele, involved in fatty acid (FA) metabolism, is a major genetic risk factor for Alzheimer’s disease (AD). This study examined the influence of APOE genotypes on blood and brain markers of the L-carnitine system, necessary for fatty acid oxidation (FAO), and their collective influence on the clinical and pathological […]
Claire J C Huguenard

APOE alleles modulate associations of plasma metabolites with variants from multiple genes on chromosome 19q13.3

November 17, 2022

The APOE ε2, ε3, and ε4 alleles differentially impact various complex diseases and traits. We examined whether these alleles modulated associations of 94 single-nucleotide polymorphisms (SNPs) harbored by 26 genes in 19q13.3 region with 217 plasma metabolites using Framingham Heart Study data. The analyses were performed in the E2 (ε2ε2 or ε2ε3 genotype), E3 (ε3ε3 […]
Alireza Nazarian

Radiosynthesis of 20-[¹⁸F]fluoroarachidonic acid for PET-MR imaging: Biological evaluation in APOE ε4–TR mice

November 7, 2022

Dysreglulated brain arachidonic acid (AA) metabolism is involved in chronic inflammation and is influenced by apolipoprotein E4 (APOE ε4) genotype, the strongest genetic risk factor of late-onset Alzheimer’s disease (AD). Visualization of AA uptake and distribution in the brain can offer insight into neuroinflammation and AD pathogenesis. Here we present a novel synthesis and radiosynthesis of […]
Juno Van Valkenburgh

The omega-3 index in Alzheimer’s disease: Ready for prime time?

October 18, 2022

The omega-3 (ω-3) index is the sum of the percentages of EPA and DHA from the total fatty acids in blood. Over the past 2 decades, some of the major observational cohorts, including the Women’s Health Initiative Memory Study, Framingham Study, and the 3-City Study, reported associations between the lowest quartile of the ω-3 index and worse cognitive measures, brain MRI measurements, and greater risks of dementia. These reports raised the prospect that the ω-3 index could be used to identify persons at risk of dementia and hypothesized that raising the ω-3 index may lower the rate of cognitive decline […]
Hussein N Yassine

Eicosanoid lipidome activation in post-mortem brain tissues of individuals with APOE ε4 and Alzheimer’s dementia

October 10, 2022

CONCLUSION: These findings implicate activation of the eicosanoid lipidome in the chronic unresolved state of inflammation in AD dementia, which is increased in carriers of the APOE ε4 allele, and identify potential therapeutic targets for resolving this chronic inflammatory state.
Brandon Ebright

Uncovering mechanisms of brain inflammation in Alzheimer’s disease with APOE ε4: Application of single cell-type lipidomics

October 6, 2022

A chronic state of unresolved inflammation in Alzheimer’s disease (AD) is intrinsically involved with the remodeling of brain lipids. This review highlights the effect of carrying the apolipoprotein E ε4 allele (APOE ε4) on various brain cell types in promoting an unresolved inflammatory state. Among its pleotropic effects on brain lipids, we focus on APOE ε4‘s activation […]
Isaac Asante

Nutrition state of science and dementia prevention: recommendations of the Nutrition for Dementia Prevention Working Group

July 13, 2022

Observational studies suggest that nutritional factors have a potential cognitive benefit. However, systematic reviews of randomised trials of dietary and nutritional supplements have reported largely null effects on cognitive outcomes and have highlighted study inconsistencies and other limitations. In this Personal View, the Nutrition for Dementia Prevention Working Group presents what we consider to be […]
Hussein N Yassine

Cognitive and neuroimaging correlates of financial exploitation vulnerability in older adults without dementia: Implications for early detection of Alzheimer’s disease

July 10, 2022

Neuropathology characteristic of Alzheimer’s disease (AD) begins to accumulate years to decades before cognitive changes are clinically detectable on standard neuropsychological tests. This presents a challenge for early intervention efforts and has spurred research on the identification of behavioral correlates of early neuropathological changes. Recent evidence suggests that financial exploitation vulnerability (FEV) due to impaired […]
Laura Fenton