TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging
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 us...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Aging Brain |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589958924000306 |
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| author | Robyn A. Honea Heather Wilkins Suzanne L. Hunt Paul J. Kueck Jeffrey M. Burns Russell H. Swerdlow Jill K. Morris |
| author_facet | Robyn A. Honea Heather Wilkins Suzanne L. Hunt Paul J. Kueck Jeffrey M. Burns Russell H. Swerdlow Jill K. Morris |
| author_sort | Robyn A. Honea |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a1cd95ec59e045498157923866863d40 |
| institution | OA Journals |
| issn | 2589-9589 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Aging Brain |
| spelling | doaj-art-a1cd95ec59e045498157923866863d402025-08-20T02:06:32ZengElsevierAging Brain2589-95892025-01-01710013410.1016/j.nbas.2024.100134TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in agingRobyn A. Honea0Heather Wilkins1Suzanne L. Hunt2Paul J. Kueck3Jeffrey M. Burns4Russell H. Swerdlow5Jill K. Morris6University 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.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, USAUniversity 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, USAUniversity 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, USAUniversity 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, USAUniversity 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, USAUniversity 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, USAA 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.http://www.sciencedirect.com/science/article/pii/S2589958924000306TOMM40APOENfLpTau181AgingGFAP |
| spellingShingle | Robyn A. Honea Heather Wilkins Suzanne L. Hunt Paul J. Kueck Jeffrey M. Burns Russell H. Swerdlow Jill K. Morris TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging Aging Brain TOMM40 APOE NfL pTau181 Aging GFAP |
| title | TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging |
| title_full | TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging |
| title_fullStr | TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging |
| title_full_unstemmed | TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging |
| title_short | TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging |
| title_sort | tomm40 may mediate gfap neurofilament light protein ptau181 and brain morphometry in aging |
| topic | TOMM40 APOE NfL pTau181 Aging GFAP |
| url | http://www.sciencedirect.com/science/article/pii/S2589958924000306 |
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