The DOI matches its Crossref record; 88 of the 89 references it cites were found in a registry or an index.
Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication
Open accessAbstract
Defects in mitochondrial oxidative phosphorylation have frequently been associated with Alzheimer's disease (AD), and both inherited and somatic mtDNA mutations have been reported in certain AD cases. To determine whether mtDNA mutations contribute more generally to the etiology of AD, we have investigated the sequence of the mtDNA control region (CR) from AD brains for possible disease-causing mutations. Sixty-five percent of the AD brains harbored the T414G mutation, whereas this mutation was absent from all controls. Moreover, cloning and sequencing of the mtDNA CR from patient and control brains revealed that all AD brains had an average 63% increase in heteroplasmic mtDNA CR mutations and that AD brains from patients 80 years and older had a 130% increase in heteroplasmic CR mutations. In addition, these mutations preferentially altered known mtDNA regulatory elements. Certain AD brains harbored the disease-specific CR mutations T414C and T477C, and several AD brains between 74 and 83 years of age harbored the CR mutations T477C, T146C, and T195C, at levels up to 70-80% heteroplasmy. AD patient brains also had an average 50% reduction in the mtDNA L-strand ND6 transcript and in the mtDNA/nuclear DNA ratio. Because reduced ND6 mRNA and mtDNA copy numbers would reduce brain oxidative phosphorylation, these CR mutations could account for some of the mitochondrial defects observed in AD.
Overview
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
Verification
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 cited source says what the claim attributes to it.
In the citing paper
“which has been described in an AD brain [169,170] in which base deletions correlate with complex IV deficiency in an AD hippocampus [171].”
From Mitochondrial Oxidative and Nitrosative Stress and Alzheimer Disease (2020) · cites this paper as [170]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The genetical theory of natural selection
Fisher, R. A. (1930) · doi:10.5962/bhl.title.27468 · Cited by 17,617
Natural Selection of Parental Ability to Vary the Sex Ratio of Offspring
Trivers, R. L., & Willard, D. E. (1973) · Science · doi:10.1126/science.179.4068.90 · Cited by 3,822
Hamilton, W. D. O. (1967) · Science · doi:10.1126/science.156.3774.477 · Cited by 3,605
Charnov, E. L. (1982) · PubMed · Cited by 2,886
Identification Guide to European Passerines
Sevensson, L. (1975) · Medical Entomology and Zoology · Cited by 2,561
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303
Huang, X., Atwood, C., Hartshorn, M. A., Multhaup, G., Goldstein, L. E., Scarpa, R. C., Cuajungco, M. P., Gray, D. N., Lim, J. T., Moir, R. D., et al. (1999) · Biochemistry · doi:10.1021/bi990438f · Cited by 1,117
MITOCHONDRIAL DNA MAINTENANCE IN VERTEBRATES
Shadel, G. S., & Clayton, D. A. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.409 · Cited by 1,059
Tracing European Founder Lineages in the Near Eastern mtDNA Pool
Richards, M. B., Macaulay, V. A., Hickey, E., Vega, E., Sykes, B. C., Guida, V., Rengo, C., Sellitto, D., Cruciani, F., Kivisild, T., et al. (2000) · The American Journal of Human Genetics · doi:10.1016/s0002-9297(07)62954-1 · Cited by 952
Sex Ratio and Local Resource Competition in a Prosimian Primate
Clark, A. B. (1978) · Science · doi:10.1126/science.201.4351.163 · Cited by 910
Research works printed but not linked: 1
- Gibson, G. E. & Huang, H. M. (2002) Front. Biosci. 7, d1007-d1015.11897553
Cited by
Sorted by citations
Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455
Self-citationIntegrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657
Oxidative stress and mitochondrial dysfunction in Alzheimer’s disease
Wang, X., Wang, W., Li, L., Perry, G., Lee, H.-G., & Zhu, X. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.10.015 · Cited by 1,357
Oxidative stress, mitochondrial damage and neurodegenerative diseases.
Guo, C., Sun, L., Chen, X., & Zhang, D. (2013) · PubMed · doi:10.3969/j.issn.1673-5374.2013.21.009 · Cited by 1,371
Mitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306
Metadata
- Authors
- Coskun, P. E., Beal, M. F., & Wallace, D. C.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Wallace, Douglas C.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2004-07-09
- Volume
- 101
- Issue
- 29
- Pages
- 10726-10731
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC490002
- OpenAlex
- W2126773395
- Cited by
- 556
- References
- 89
- Citations by year
- 2026: 13 · 2025: 16 · 2024: 14 · 2023: 18 · 2022: 35 · 2021: 38 · 2020: 28 · 2019: 25 · 2018: 18 · 2017: 16 · 2016: 23 · 2015: 15 · 2014: 19 · 2013: 30 · 2012: 24
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- Emory University
- National Institutes of Health
- University of California, Irvine
- National Institute on Aging (R01AG020729, AG-13154, AG 20729, R01AG013154)
- National Institute of Neurological Disorders and Stroke (NS-21328, R01NS021328)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, mitochondrial DNA, mitochondrial DNA control region, somatic mutations, heteroplasmy, mitochondrial transcription, mitochondrial DNA replication, oxidative phosphorylation, mitochondrial DNA copy number, brain aging
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, DNA Mutational Analysis, DNA Replication, DNA, Mitochondrial, Humans, Mutation, Oxidative Phosphorylation, Transcription, Genetic, Locus Control Region
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
