TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging
Robyn A. Honea,
Heather Wilkins,
Suzanne L. Hunt,
Paul J. Kueck,
Jeffrey M. Burns,
Russell H. Swerdlow,
Jill K. Morris
Affiliations
Robyn A. Honea
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, 66160, USA; Corresponding author at: KU Alzheimer’s Disease Research Center, University of Kansas Medical Center, 4350 Shawnee Mission Parkway, MS 6002, Fairway, KS 66205, USA.
Heather Wilkins
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, 66160, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
Suzanne L. Hunt
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Biostatistics and Data Science, University of Kansas Medical Center, Kansas City, KS, 66160, USA
Paul J. Kueck
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, 66160, USA
Jeffrey M. Burns
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, 66160, USA
Russell H. Swerdlow
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, 66160, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
Jill K. Morris
University of Kansas Alzheimer’s Disease Research Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA; Department of Neurology, University of Kansas School of Medicine, Kansas City, KS, 66160, USA; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA
A growing amount of data has implicated the TOMM40 gene in the risk for Alzheimer’s disease (AD), neurodegeneration, and accelerated aging. No studies have investigated the relationship of TOMM40 rs2075650 (‘650) on the structural complexity of the brain or plasma markers of neurodegeneration. We used a comprehensive approach to quantify the impact of TOMM40 ‘650 on brain morphology and multiple cortical attributes in cognitively unimpaired (CU) individuals. We also tested whether the presence of the risk allele, G, of TOMM40 ‘650 was associated with plasma markers of amyloid, tau, and neurodegeneration and if there were interactions with age and sex, controlling for the effects of APOE ε4. We found that the TOMM40 ‘650 G-allele was associated with decreased sulcal depth, increased gyrification index, and decreased gray matter volume. NfL, GFAP, and pTau181 had independent and age-associated increases in individuals with a G-allele. Our data suggest that TOMM40 ‘650 is associated with aging-related plasma biomarkers and brain structure variation in temporal-limbic circuits.
