Targeted Lipidomics To Measure Phospholipids and Sphingomyelins in Plasma: A Pilot Study To Understand the Impact of Race/Ethnicity in Alzheimer’s Disease

Abstract

The number of people suffering from Alzheimer’s disease (AD) is increasing rapidly every year. One aspect of AD that is often overlooked is the disproportionate incidence of AD among African American/Black populations. With the recent development of novel assays for lipidomics analysis in recent times, there has been a drastic increase in the number of studies focusing on changes of lipids in AD. However, very few of these studies have focused on or even included samples from African American/Black individuals samples. In this study, we aimed to determine if the lipidome in AD is universal across non-Hispanic White and African American/Black individuals. To accomplish this, a targeted mass spectrometry lipidomics analysis was performed on plasma samples (N = 113) obtained from cognitively normal (CN, N = 54) and AD (N = 59) individuals from African American/Black (N = 56) and non-Hispanic White (N = 57) backgrounds. Five lipids (PS 18:0_18:0, PS 18:0_20:0, PC 16:0_22:6, PC 18:0_22:6, and PS 18:1_22:6) were altered between AD and CN sample groups (p value < 0.05). Upon racial stratification, there were notable differences in lipids that were unique to African American/Black or non-Hispanic White individuals. PS 20:0_20:1 was reduced in AD in samples from non-Hispanic White but not African American/Black adults. We also tested whether race/ethnicity significantly modified the association between lipids and AD status by including a race × diagnosis interaction term in a linear regression model. PS 20:0_20:1 showed a significant interaction (p = 0.004). The discovery of lipid changes in AD in this study suggests that identifying relevant lipid biomarkers for diagnosis will require diversity in sample cohorts.

Relationship Between Sphingomyelin and Risk of Alzheimer’s Disease: A Bidirectional Mendelian Randomization Study

“…However, results remain inconsistent, and the precise causal relationship has been debated, with contradictions across various studies. While some investigations have found increased SM levels in AD patients [7,8], others have shown decreased SM levels [9][10][11] or no change at all [12]. Such disparities could be attributed to the varying sample sizes, research methodologies, regional and ethnic diversities, and other confounding factors of these studies.…”

Brain cholesterol and Alzheimer's disease: challenges and opportunities in probe and drug development

“…While the discussion of the distinct lipid classes is beyond the scope of this review, evidence to date points towards a broad involvement of dysfunctional lipid metabolism that goes far beyond neural cholesterol. Of note, the contemporary lipidomics landscape in AD has recently been reviewed by various other groups [76][77][78][79][80][81][82] .…”

Deciphering ApoE Genotype-Driven Proteomic and Lipidomic Alterations in Alzheimer’s Disease Across Distinct Brain Regions

“…While experiments investigating how AD is biased by genetic information in addition to race, sex, and age have been explored previously, a majority of this research field is brain region-specific or focused on downstream cerebrospinal fluid (CSF) and/or plasma changes. ,− Global investigations of brain region perturbations associated with AD have identified novel mechanisms of disease progression based on differences in region morphology and function, providing another key component toward developing a comprehensive understanding of AD pathophysiology. ,,, Investigations of AD across brain regions have, however, largely overlooked the CBM region, thereby leaving a hole in our understanding of global AD progression throughout the brain. This has also resulted in regional influences of confounding factors such as APOE allele type in AD progression and molecular predisposition of ε4 alleles being unknown.…”