The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Alzheimer disease, the two-hit hypothesis: An update
Open accessAbstract
Given the relative modality of single-insult models to accurately reflect Alzheimer disease pathogenesis, based on studies on mitogenic and oxidative stress signaling pathways, we proposed a two-hit hypothesis 2 years ago stating that both oxidative stress and mitogenic dysregulation are necessary and sufficient to cause the disease and suggested that it may be a common mechanism for other neurodegenerative diseases as well (X. Zhu, A.K. Raina, G. Perry, M.A. Smith, Alzheimer's disease: the two-hit hypothesis, Lancet Neurol. 3 (2004) 219-226). Recent developments in the field confirm some important predictions of the hypothesis and shed new lights on potential mechanisms regarding how steady state may be achieved in sporadic AD cases and therefore, in our opinion, strengthen the hypothesis, which will be the focus of this review.
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.
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
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease
Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman, M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704243361704 · Cited by 2,380
RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease
Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., et al. (1996) · Nature · doi:10.1038/382685a0 · Cited by 2,012
Oxidative Damage Is the Earliest Event in Alzheimer Disease
Nunomura, A., Perry, G., Aliev, G., Hirai, K., Takeda, A., Balraj, E. K., Jones, P. K., Ghanbari, H., Wataya, T., Shimohama, S., et al. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.8.759 · Cited by 1,885
Self-citationExcess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease.
Smith, C. D., Carney, J. M., Starke-Reed, P. E., Oliver, C. N., Stadtman, E. R., Floyd, R. A., & Markesbery, W. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10540 · Cited by 1,296
Risk of Alzheimer's disease and duration of NSAID use
Stewart, W. F., Kawas, C., Corrada, M., & Metter, E. J. (1997) · Neurology · doi:10.1212/wnl.48.3.626 · Cited by 1,132
Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. A., & Butterfield, D. A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.8.3270 · Cited by 1,086
Oxidative stress in Alzheimer’s disease
Smith, M. A., Rottkamp, C. A., Nunomura, A., Raina, A. K., & Perry, G. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00040-5 · Cited by 895
Praticò, D., Uryu, K., Leight, S., Trojanoswki, J. Q., & Lee, V. M.-Y. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-12-04183.2001 · Cited by 777
Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils
Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D. (1996) · Nature · doi:10.1038/382716a0 · Cited by 727
Cited by
Oxidative Stress and Neurotoxicity
Sayre, L. M., Perry, G., & Smith, M. A. (2008) · Chemical Research in Toxicology · doi:10.1021/tx700210j · Cited by 867
Self-citationAutophagy failure in Alzheimer's disease—locating the primary defect
Nixon, R. A., & Yang, D.-S. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.01.021 · Cited by 595
Adibhatla, R. M., & Hatcher, J. F. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2668 · Cited by 480
de Vries, H. E., Witte, M., Hondius, D., Rozemuller, A. J. M., Drukarch, B., Hoozemans, J., & van Horssen, J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.09.001 · Cited by 428
Smith, M. A., Zhu, X., Tabaton, M., Liu, G., McKeel, D. W., Cohen, M. L., Wang, X., Siedlak, S. L., Dwyer, B. E., Hayashi, T., et al. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-1239 · Cited by 401
Self-citation
Metadata
- Authors
- Zhu, X., Lee, H.-G., Perry, G., & Smith, M. A.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 1772
- Issue
- 4
- Pages
- 494-502
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W2154566941
- Cited by
- 292
- References
- 24
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Alzheimer disease, the two-hit hypothesis: An update. https://app.cochat.ai/papers/10.1016/j.bbadis.2006.10.014
- The paper
- Zhu, X., Lee, H.-G., Perry, G., & Smith, M. A. (2007). Alzheimer disease, the two-hit hypothesis: An update. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. https://doi.org/10.1016/j.bbadis.2006.10.014
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
