Interplay of Dietary Amino Acids, Metabolic Syndrome, and ApoE ε4 on Brain Integrity at Midlife

1139 

Abstract Submission 

Cherry Youn¹, Barbara Strasser², Dietmar Fuchs³, Drew Gourley⁴, Marie Caillaud¹, Yanrong Li¹, Isabelle Gallagher¹, Hirofumi Tanaka⁴, Andreana Haley¹

¹Department of Psychology, University of Texas at Austin, Austin, TX, ²Sigmund Freud University Vienna, Vienna, Vienna, ³Institute of Biological Chemistry, Biocentre, Innsbruck, Innsbruck, ⁴Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX

Cherry Youn  
Department of Psychology, University of Texas at Austin
Austin, TX

Barbara Strasser  
Sigmund Freud University Vienna
Vienna, Vienna

Dietmar Fuchs  
Institute of Biological Chemistry, Biocentre
Innsbruck, Innsbruck

Drew Gourley  
Department of Kinesiology and Health Education, University of Texas at Austin
Austin, TX

Marie Caillaud  
Department of Psychology, University of Texas at Austin
Austin, TX

Yanrong Li  
Department of Psychology, University of Texas at Austin
Austin, TX

Isabelle Gallagher  
Department of Psychology, University of Texas at Austin
Austin, TX

Hirofumi Tanaka  
Department of Kinesiology and Health Education, University of Texas at Austin
Austin, TX

Andreana Haley  
Department of Psychology, University of Texas at Austin
Austin, TX

Understanding the nuanced interactions between dietary components and genetic factors is critical in deciphering the mechanisms of neural aging. Tryptophan (TRP) and phenylalanine (PHE) are direct precursors of kynurenine (KYN) and tyrosine (TYR), respectively, and are large neutral amino acids (LNAA) that have been implicated in the pathogenesis of neurodegenerative diseases1. Their role in neurotransmitter synthesis suggests a complex interplay with cognitive function. Moreover, metabolic syndrome (MetS) has been recognized as a catalysis for accelerated cognitive decline, potentially exacerbating the aging process. This relationship may be even more pronounced in the presence of the apolipoprotein E ε4 (ApoE4) allele, a well-established genetic risk factor for Alzheimer's disease2,3. Despite the significant strides in identifying the deleterious effects of these variables on cognitive performance, the research remains fragmented, especially regarding the effects of LNAA on brain health across different life stages, vascular risk, and genetic backgrounds. Hence, our study aims to bridge this gap by exploring the intersection of LNAA levels, MetS, brain integrity, and the presence of the ApoE4 allele at midlife.

65 adults aged 40-61 underwent a health assessment. All concentrations of LNAA were determined by high-performance liquid chromatography. The number of MetS components was calculated according to the unified criteria4. MRI was conducted on a Siemens 3T Skyra with a 32-channel head coil. Fluid-attenuated inversion recovery images and high-resolution structural images were acquired to determine white matter hyperintensity (WMH) volume, which was quantified using the Lesion Segmentation Tool in SPM8. ApoE genotyping was conducted using polymerase chain reaction amplification and Sanger sequencing5. Participants grouped into two: individuals carrying 1 or 2 copies of the ApoE ε4 allele (ApoE ε4 positive) or those not carrying any copy (ApoE ε4 negative). Multivariate linear regression analyses were performed using R to test the joint effect of LNAA, MetS, and ApoE4 on white matter integrity in middle-aged adults. Sex, age, and years of education were included as covariates.

Multivariate linear regression analyses for assessing 3-way interaction effects indicated that the ApoE ε4 allele was a significant factor in WMH volume. Interestingly, MetS was not a significant predictor of WMH volume in participants without the ApoE ε4 allele. This suggests that MetS alone does not markedly affect neural integrity in the absence of genetic susceptibility. Furthermore, LNAA levels did not moderate the non-significant relationship between MetS and WMH volume in these individuals. However, among ApoE ε4 carriers, LNAA levels played a moderating role, over and above relevant covariates. Specifically, low LNAA levels were associated with low WMH volume in the context of MetS (p <0.01). Moreover, higher LNAA appeared to accelerate the negative neural impact of MetS in these genetically at-risk individuals, revealing a nutrient-genetic interaction that may be pivotal for targeted dietary interventions.

This study elucidates the complex interplay of genetic predisposition, metabolic factors, and dietary amino acids on neural health. We discovered that MetS alone did not impact white matter integrity, nor did LNAA levels, in individuals without the ApoE ε4 allele. However, for ApoE ε4 carriers, LNAA levels substantially moderated WMH volume, particularly in the presence of MetS. Low LNAA levels correlated with low WMH, whereas higher levels attenuated MetS-related brain impairment. These insights underscore the potential of LNAA management as a strategic approach to mitigate the risks associated with MetS, especially in individuals genetically susceptible to neurodegeneration. Future dietary recommendations could be personalized to optimize cerebrovascular health in midlife, considering one's metabolic and genetic profiles.

Genetics Other

Aging ¹

Lifespan Development Other

White Matter Anatomy, Fiber Pathways and Connectivity ²

Physiology, Metabolism and Neurotransmission Other

ADULTS

Aging

MRI

Multivariate

White Matter

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC