The DOI matches its Crossref record; 158 of the 158 references it cites were found in a registry or an index.
Amyloid Precursor Protein Processing and Alzheimer's Disease
Open accessAbstract
Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (APP) proteolysis is the crucial step in the development of AD. APP is a single-pass transmembrane protein expressed at high levels in the brain and metabolized in a rapid and highly complex fashion by a series of sequential proteases, including the intramembranous γ-secretase complex, which also process other key regulatory molecules. Why Aβ accumulates in the brains of elderly individuals is unclear but could relate to changes in APP metabolism or Aβ elimination. Lessons learned from biochemical and genetic studies of APP processing will be crucial to the development of therapeutic targets to treat AD.
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“Mutations in APP are causal for Alzheimer's disease with abnormal processing of APP and the generation of toxic amyloid-β aggregates hallmarks of Alzheimer's pathology [89].”
From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [89]
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“Changes in APP processing and the formation of toxic amyloid-β aggregates are a key characteristic of Alzheimer's disease pathology [89].”
From Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling (2026) · cites this paper as [89]
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“β-amyloid (Aβ) protein is the principal component of AD-associated amyloid plaques, and is produced by protease cleavage of the type I transmembrane amyloid precursor protein (APP) [16, 17].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [17]
In the citing paper
“In Alzheimer’s disease a series of cleavage events lead to several shorter soluble forms of amyloid precursor protein (sAPPα, sAPPβ), C-terminal fragments (AICD50, CTF 83, CTF 89, CTF 99, p3) and amyloid-beta peptides, which contribute to forming the characteristic plaques observed in the brains of diseased individuals.(10)”
From Putting humpty dumpty back together again: what does protein quantification mean in bottom-up proteomics? (2022) · cites this paper as [10]
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Citations
Cites
2 retracted
RETRACTED ARTICLE: APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
Nikolaev, A., McLaughlin, T., O’Leary, D. D. M., & Tessier-Lavigne, M. (2009) · Nature · doi:10.1038/nature07767 · Cited by 992
RetractedRETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10
Dönmez, G., Wang, D., Cohen, D. E., & Guarente, L. (2010) · Cell · doi:10.1016/j.cell.2010.06.020 · Cited by 443
RetractedGlenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619
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Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Forecasting the global burden of Alzheimer's disease
Brookmeyer, R., Johnson, E., Ziegler‐Graham, K., & Arrighi, H. M. (2007) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2007.04.381 · Cited by 3,370
Neurodegenerative Diseases Target Large-Scale Human Brain Networks
Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L., & Greicius, M. D. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.024 · Cited by 2,350
Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury
McKee, A. C., Cantu, R. C., Nowinski, C. J., Hedley-Whyte, E. T., Gavett, B. E., Budson, A. E., Santini, V. E., Lee, H.-S., Kubilus, C. A., & Stern, R. A. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181a9d503 · Cited by 2,295
A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., et al. (1999) · Nature · doi:10.1038/19083 · Cited by 2,100
Research works printed but not linked: 4
- 10.1172/JCI20640 · DOI · Paper page
- Rohn TT, 2009, Int. J. Clin. Exp. Pathol., 2, 108
- Rohn TT, 2009, Int. J. Clin. Exp. Med., 2, 300
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Cited by
Sorted by citations
The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329
“There are many reviews describing the generation of Aβ peptides [32], and these pathways remain viable therapeutic targets.”
BackgroundInflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253
“The function of APP is unknown but is believed to have a role in cell health and growth [5].”
BackgroundApolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
Yamazaki, Y., Zhao, N., Caulfield, T. R., Liu, C.-C., & Bu, G. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0228-7 · Cited by 1,425
Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics
Tiwari, S., Atluri, V., Kaushik, A., Yndart, A., & Nair, M. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s200490 · Cited by 1,308
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138
“78,111,112 115 However, FAD mutations are not necessarily linked to an increase in A β 42 levels or an elevation of A β 42 /A β 40 ratio.”
Background
Metadata
- Authors
- O'Brien, R. J., & Wong, P. C.
- Affiliations
- Department of Neurology, Johns Hopkins Bayview Medical Center
- Johns Hopkins University (US)
- ORCID
- Wong, Philip C.
- Venue
- Annual Review of Neuroscience
- Publisher
- Annual Reviews
- Published
- 2011-07-21
- Volume
- 34
- Issue
- 1
- Pages
- 185-204
- ISSN
- 0147-006X (ISSN-L)
- 1545-4126
- PMC
- PMC3174086
- OpenAlex
- W2129085204
- Cited by
- 2,061
- References
- 158
- Citations by year
- 2026: 118 · 2025: 182 · 2024: 227 · 2023: 194 · 2022: 197 · 2021: 225 · 2020: 185 · 2019: 143 · 2018: 144 · 2017: 105 · 2016: 91 · 2015: 76 · 2014: 70 · 2013: 63 · 2012: 33
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P50AG005146)
- Topics
- 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
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid precursor protein, APP processing, amyloid-beta, gamma-secretase, intramembrane proteolysis, tau hyperphosphorylation, amyloid accumulation, APP metabolism, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Models, Biological, Amyloid beta-Protein Precursor, Amyloidogenic Proteins
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