TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trial
Open accessAbstract
A number of recent studies have not replicated the association of the translocase of the outer mitochondrial membrane pore subunit (TOMM40) rs10524523 polymorphism, which is in linkage disequilibrium with apolipoprotein E (APOE), with age of onset of Alzheimer's disease (AD). This perspective describes the differences between these later studies and the original experiments. We highlight the necessity for using standardized and informative assessment tools and processes when determining the age of development of AD or AD symptoms, and also stress that this clinical phenotype is best measured reliably in prospective studies during which subjects are monitored over time. This is true when assessing potential biomarkers for age of onset and when assessing the therapeutic potential of medicines that may delay the onset or progression of this disease.
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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 [152]
Cites
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 · cited 1× · see citing works
“The genotype combination as a predictor of age-dependent risk of cognitive decline will be validated in a prospective study, using standardized clinical assessments for identifying onset of MCI resulting from AD [10], uniformly conducted by trained clinicians at defined time intervals, and using a technically validate…”
MethodMorris, J. C., Weintraub, S., Chui, H. C., Cummings, J., DeCarli, C., Ferris, S., Foster, N. L., Galasko, D., Graff-Radford, N., Peskind, E. R., et al. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213865.09806.92 · Cited by 950 · see citing works
The Alzheimer's Disease Centers' Uniform Data Set (UDS)
Weıntraub, S., Salmon, D. P., Mercaldo, N. D., Ferris, S. H., Graff‐Radford, N. R., Chui, H. C., Cummings, J. L., DeCarli, C. S., Foster, N. L., Galasko, D. R., et al. (2009) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e318191c7dd · Cited by 885 · see citing works
Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease
Li, H., Wetten, S., Li, L., St. Jean, P. L., Upmanyu, R., Surh, L., Hosford, D., Barnes, M. R., Briley, J. D., Borrie, M., et al. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.3 · Cited by 499 · see citing works
Self-citationA 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-citationCruchaga, C. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.155 · Cited by 104 · see citing works
Comprehensive Search for Alzheimer Disease Susceptibility Loci in the APOE Region
Jun, G., Vardarajan, B. N., Buros, J. L., Yu, C., Hawk, M., Dombroski, B. A., Crane, P. K., Larson, E. B., Mayeux, R. P., Haines, J. L., et al. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.2052 · Cited by 103 · see citing works
TOMM40 Association With Alzheimer Disease
Guerreiro, R. J., & Hardy, J. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.1935 · Cited by 31 · see citing works
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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
Pioglitazone for the treatment of Alzheimer’s disease
Galimberti, D., & Scarpini, E. (2017) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2017.1265504 · Cited by 106 · see citing works
Roses, A., Sundseth, S., Saunders, A., Gottschalk, W., Burns, D., & Lutz, M. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.015 · Cited by 70 · see citing works
Self-citationA 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-citationMitochondrial Function and Neurodegenerative Diseases
Wilkins, H. M., Weidling, I., Koppel, S., Wang, X., von Schulze, A., & Swerdlow, R. H. (2018) · The Molecular and Cellular Basis of Neurodegenerative Diseases · doi:10.1016/b978-0-12-811304-2.00013-4 · Cited by 2 · see citing works
- Authors
- Roses, A. D., Lutz, M. W., Crenshaw, D. G., Grossman, I., Saunders, A. M., & Gottschalk, W. K.
- Affiliations
- Duke University (US)
- IsraGene Ltd Rosh HaAyin Israel
- Corresponding author
- Roses, Allen D.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2013-01-21
- Volume
- 9
- Issue
- 2
- Pages
- 132-136
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2129703004
- Cited by
- 63
- References
- 9
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 10 · 2015: 7 · 2014: 12 · 2013: 4
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- TOMM40, apolipoprotein E
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, Alzheimer Disease, Apolipoproteins E, Clinical Trials as Topic, Genotype, Humans, Phenotype, Linkage Disequilibrium, Age of Onset, Polymorphism, Single Nucleotide, Membrane Transport Proteins
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