Date

1-4-2016 12:00 AM

Major

Nutritional Science

Department

Food Science & Human Nutrition

College

College of Human Sciences

Project Advisor

Auriel Willette

Project Advisor's Department

Food Science & Human Nutrition

Description

Objective: To delineate novel relationships between Alzheimer disease (AD) factors, such as Translocase of the Outer Mitochondrial Membrane - kD 40 (TOMM40) genotype, AD family history (FH), vascular risk factors, and vascular neuropathology Methods: We performed linear mixed model regression on imaging and biomarker data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Among 210 healthy adults with 1 or 2 Apolipoprotein ε4 (APOE4) alleles, we stratified by TOMM40 genotypes S/L, L/L, L/VL. Main effects and interactions between TOMM40 and FH were conducted on white matter hyperintensities (WMH), infarctions, and total intracranial volume. Vascular risk factors homocysteine and cholesterol were similarly tested, adjusting for age, gender, BMI and hyperglycemia status. Results: FH*TOMM40 interactions showed that L/L and L/VL genotypes exercised “beneficial” effects for FH negative (FH-) and “detrimental” effects for FH positive (FH+) participants. In FH+, risk alleles were associated with higher homocysteine (P=0.024), total cholesterol (P=0.005), infarction occurrence (P=0.045), greater WMH burden (P = 0.032) and smaller intracranial volume (P<0.001). Conclusions: These results suggest FH modulates TOMM40’s effects on vascular markers and AD neurovascular pathology in APOE4 individuals. These interactions between FH and TOMM40 influence neuropathology, suggesting TOMM40 genotype could serve as a novel predictor for AD.

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Apr 1st, 12:00 AM

Genetic Haplotypes and Family History of Alzheimer’s disease Modify Homocysteine and Influence Neurovascular Pathology

Objective: To delineate novel relationships between Alzheimer disease (AD) factors, such as Translocase of the Outer Mitochondrial Membrane - kD 40 (TOMM40) genotype, AD family history (FH), vascular risk factors, and vascular neuropathology Methods: We performed linear mixed model regression on imaging and biomarker data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Among 210 healthy adults with 1 or 2 Apolipoprotein ε4 (APOE4) alleles, we stratified by TOMM40 genotypes S/L, L/L, L/VL. Main effects and interactions between TOMM40 and FH were conducted on white matter hyperintensities (WMH), infarctions, and total intracranial volume. Vascular risk factors homocysteine and cholesterol were similarly tested, adjusting for age, gender, BMI and hyperglycemia status. Results: FH*TOMM40 interactions showed that L/L and L/VL genotypes exercised “beneficial” effects for FH negative (FH-) and “detrimental” effects for FH positive (FH+) participants. In FH+, risk alleles were associated with higher homocysteine (P=0.024), total cholesterol (P=0.005), infarction occurrence (P=0.045), greater WMH burden (P = 0.032) and smaller intracranial volume (P<0.001). Conclusions: These results suggest FH modulates TOMM40’s effects on vascular markers and AD neurovascular pathology in APOE4 individuals. These interactions between FH and TOMM40 influence neuropathology, suggesting TOMM40 genotype could serve as a novel predictor for AD.