A homopolymer polymorphism in the TOMM40 gene contributes to cognitive performance in aging
Open accessAbstract
INTRODUCTION: A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer's disease risk and age of onset. OBJECTIVE: To explore the effects of the polymorphic polyT tract (rs10524523, referred as '523') on cognitive performance in cognitively healthy elderly individuals. METHODS: One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent was obtained, and participants completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery, and the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected for determination of the TOMM40 '523' (S, L, VL) and the apolipoprotein E (APOE) (ɛ2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were eligible for the association analysis. Participants were divided into three groups based on '523' genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized linear models were used to evaluate the association between the '523' genotypes and neuropsychological test performance. Analyses were adjusted for age, sex, education, depression, and APOE ɛ4 status. A planned subanalysis was undertaken to evaluate the association between '523' genotypes and test performance in a sample restricted to APOE ɛ3 homozygotes. RESULTS: The S homozygotes performed better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL genotype groups on measures associated with memory (CANTAB Paired Associates Learning, Verbal Recognition Memory free recall) and executive function (CANTAB measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE ɛ3 homozygotes only showed that the S/S group performed significantly better than the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual Information Processing latency), and executive function (Digit Symbol Substitution). The S/S group performed marginally better than the VL/VL group on Intra-Extra Dimensional Set Shift. None of the associations remained significant after applying a Bonferroni correction for multiple testing. CONCLUSIONS: Results suggest important APOE-independent associations between the TOMM40 '523' polymorphism and specific cognitive domains of memory and executive control that are preferentially affected in early-stage Alzheimer's disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The TOMM40 gene, and by extension its protein product, could potentially impact LOAD.
“from a strict association perspective it does appear that the TOMM40 gene, and by extension its protein product, could potentially impact LOAD.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [146]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Tabachnick, B. G., & Fidell, L. S. (1983) · Cited by 79,888 · see citing works
The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53221.x · Cited by 25,553 · see citing works
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · see citing works
VALIDITY OF THE TRAIL MAKING TEST AS AN INDICATOR OF ORGANIC BRAIN DAMAGE
Reitan, R. M. (1958) · Perceptual and Motor Skills · doi:10.2466/pms.1958.8.3.271 · Cited by 7,925 · see citing works
Association of apolipoprotein E allele ϵ4 with late‐onset familial and sporadic Alzheimer's disease
Saunders, A. M., Strittmatter, W. J., Schmechel, D., St. George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R., Alberts, M. J., et al. (1993) · Neurology · doi:10.1212/wnl.43.8.1467 · Cited by 3,786 · see citing works
Self-citationLuis, C. A., Keegan, A. P., & MULLAN, M. J. (2008) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2101 · Cited by 511 · see citing works
Grober, E. H., Hall, C. B., Lipton, R. B., Zonderman, A. B., Resnick, S. M., & Kawas, C. H. (2008) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617708080302 · Cited by 424 · see citing works
A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease
Roses, A. D., Lutz, M. W., Amrine‐Madsen, H., Saunders, A. M., Crenshaw, D. G., Sundseth, S. S., Huentelman, M. J., Welsh-Bohmer, K. A., & Reiman, E. M. (2009) · The Pharmacogenomics Journal · doi:10.1038/tpj.2009.69 · Cited by 391 · see citing works
Self-citationMultiple cognitive deficits during the transition to Alzheimer's disease
Bäckman, L., Jones, S., Berger, A., Laukka, E. J., & Small, B. J. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01386.x · Cited by 293 · see citing works
Deelen, J., Beekman, M., Uh, H., Helmer, Q., Kuningas, M., Christiansen, L., Kremer, D., van der Breggen, R., Suchiman, H. E. D., Lakenberg, N., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00705.x · Cited by 280 · see citing works
Attention and working memory deficits in mild cognitive impairment
Saunders, N. L., & Summers, M. (2009) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390903042379 · Cited by 186 · see citing works
Koch, W., Ehrenhaft, A., Grießer, K., Pfeufer, A., Mueller, J. C., Schömig, A., & Kastrati, A. (2002) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2002.197 · Cited by 169 · see citing works
Multiple Cognitive Deficits in Amnestic Mild Cognitive Impairment
Kramer, J. H., Nelson, A., Johnson, J. K., Yaffe, K. S., Glenn, S., Rosen, H. J., & Miller, B. L. (2006) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000095303 · Cited by 144 · see citing works
Johnson, S. C., La Rue, A., Hermann, B. P., Xu, G., Koscik, R. L., Jonaitis, E. M., Bendlin, B. B., Hogan, K. J., Roses, A. D., Saunders, A. M., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2010.11.012 · Cited by 112 · see citing works
Self-citationGenetic variation at a single locus and age of onset for Alzheimer's disease
Lutz, M. W., Crenshaw, D. G., Saunders, A. M., & Roses, A. D. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.01.011 · Cited by 101 · see citing works
Self-citationMild Cognitive Impairment: Deficits in Cognitive Domains Other than Memory
Ribeiro, F., de Mendonça, A., & Guerreiro, M. (2006) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000091435 · Cited by 100 · see citing works
The Measurement of Creativity by the Stroop Color and Word Test
Golden, C. J. (1975) · Journal of Personality Assessment · doi:10.1207/s15327752jpa3905_9 · Cited by 91 · see citing works
Genetic Regulation of α-Synuclein mRNA Expression in Various Human Brain Tissues
Linnertz, C. L., Saucier, L., Ge, D., Cronin, K. D., Burke, J. R., Browndyke, J. N., Hulette, C. M., Welsh-Bohmer, K. A., & Chiba‐Falek, O. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007480 · Cited by 88 · see citing works
Self-citationIdentification of VaD and AD prodromes: The Cache County Study
Hayden, K. M., Warren, L. H., Pieper, C. F., Østbye, T., Tschanz, J. T., Norton, M. C., Breitner, J. C. S., & Welsh-Bohmer, K. A. (2005) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2005.06.002 · Cited by 22 · see citing works
Self-citationP1‐096: TOMM40, APOE, and age of onset of Alzheimer's disease
Caselli, R. J., Saunders, A. M., Lutz, M. W., et al. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.05.644 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Using genetics to enable studies on the prevention of Alzheimer's disease
Crenshaw, D. G., Gottschalk, W. K., Lutz, M. W., Grossman, I., Saunders, A. M., Burke, J. R., Welsh-Bohmer, K. A., Brannan, S. K., Burns, D. K., & Roses, A. D. (2013) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.222 · Cited by 70 · see citing works
A genetics-based biomarker risk algorithm for predicting risk of Alzheimer's disease
Lutz, M. W., Sundseth, S. S., Burns, D. K., Saunders, A. M., Hayden, K. M., Burke, J. R., Welsh‐Bohmer, K. A., Roses, A. D., & Initiative, A. D. N. (2016) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2015.12.002 · Cited by 30 · see citing works
Self-citation
- Authors
- Hayden, K. M., McEvoy, J. M., Linnertz, C., Attix, D., Kuchibhatla, M., Saunders, A. M., Lutz, M. W., Welsh‐Bohmer, K. A., Roses, A. D., & Chiba‐Falek, O.
- Affiliations
- Duke University (US)
- Duke Medical Center (US)
- Joseph and Kathleen Bryan Alzheimer's Disease Research Center Duke University Durham NC USA
- Corresponding author
- Chiba‐Falek, Ornit
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2012-08-06
- Volume
- 8
- Issue
- 5
- Pages
- 381-388
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC3438346
- OpenAlex
- W2051590969
- Cited by
- 53
- References
- 21
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 11 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 2
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (K01 AG029336)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- TOMM40
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, Aged, Aged, 80 and over, Aging, Apolipoproteins E, Cognition Disorders, Female, Genotype, Humans, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Genetic, Genetic Predisposition to Disease, Membrane Transport Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
