Amyloid Precursor Protein Trafficking, Processing, and Function
Open accessAbstract
Intracellular trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations over the past two decades. APP is the precursor to the amyloid beta-protein (Abeta), the 38-43-amino acid residue peptide that is at the heart of the amyloid cascade hypothesis of Alzheimer disease (AD). Tremendous progress has been made since the initial identification of Abeta as the principal component of brain senile plaques of individuals with AD. Specifically, molecular characterization of the secretases involved in Abeta production has facilitated cell biological investigations on APP processing and advanced efforts to model AD pathogenesis in animal models. This minireview summarizes salient features of APP trafficking and amyloidogenic processing and discusses the putative biological functions of APP.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
BACE1 cleavage of APP is the rate-limiting step along the amyloidogenic processing pathway.
“BACE1 cleavage of APP is the rate-limiting step along the amyloidogenic processing pathway (Thinakaran and Koo, 2008; Zhang et al., 2011)”
From Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-β production (2020) · cites this paper as Thinakaran and Koo, 2008
Cites
A Transcriptively Active Complex of APP with Fe65 and Histone Acetyltransferase Tip60
Cao, X., & Südhof, T. C. (2001) · Science · doi:10.1126/science.1058783 · Cited by 1,202 · see citing works
Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives
Mattson, M. P. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.4.1081 · Cited by 1,006 · see citing works
Young-Pearse, T. L., Bai, J., Chang, R., Zheng, J. B., LoTurco, J. J., & Selkoe, D. J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4701-07.2007 · Cited by 369 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606 · see citing works
Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis
Karch, C. M., & Goate, A. M. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.006 · Cited by 1,357 · see citing works
Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy
Bu, G. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2620 · Cited by 1,168 · see citing works
Degradation of misfolded proteins in neurodegenerative diseases: Therapeutic targets and strategies
Ciechanover, A., & Kwon, Y. T. (2015) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.117 · Cited by 898 · see citing works
Demystifying Heparan Sulfate–Protein Interactions
Xu, D., & Esko, J. D. (2014) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060713-035314 · Cited by 805 · see citing works
Modeling familial Alzheimer's disease with induced pluripotent stem cells
Yagi, T., Ito, D., Okada, Y., Akamatsu, W., Nihei, Y., Yoshizaki, T., Yamanaka, S., Okano, H., & Suzuki, N. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr394 · Cited by 599 · see citing works
Alzheimer’s Disease Genetics: From the Bench to the Clinic
Karch, C. M., Cruchaga, C., & Goate, A. M. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.041 · Cited by 473 · see citing works
Reactive astrocytes in neurodegenerative diseases
Li, K., Li, J., Zheng, J., & Qin, S. (2019) · Aging and disease · doi:10.14336/ad.2018.0720 · Cited by 398 · see citing works
Treusch, S., Hamamichi, S., Goodman, J. L., Matlack, K. E. S., Chung, C. Y., Baru, V., Shulman, J. M., Parrado, A., Bevis, B. J., Valastyan, J. S., et al. (2011) · Science · doi:10.1126/science.1213210 · Cited by 379 · see citing works
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372 · see citing works
Sharma, P., Srivastava, P., Seth, A., Tripathi, P. N., Banerjee, A. G., & Shrivastava, S. K. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.006 · Cited by 331 · see citing works
Genes associated with Alzheimer's disease: an overview and current status
Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311 · see citing works
Microglial Aβ Receptors in Alzheimer’s Disease
Yu, Y., & Ye, R. D. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0101-6 · Cited by 247 · see citing works
Jazvinšćak Jembrek, M., Hof, P. R., & Šimić, G. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/346783 · Cited by 244 · see citing works
Kandalepas, P. C., Sadleir, K. R., Eimer, W. A., Zhao, J., Nicholson, D. A., & Vassar, R. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1152-3 · Cited by 240 · see citing works
Amyloidosis in Alzheimer’s Disease: Pathogeny, Etiology, and Related Therapeutic Directions
Ma, C., Hong, F., & Yang, S. (2022) · Molecules · doi:10.3390/molecules27041210 · Cited by 243 · see citing works
Djelti, F., Braudeau, J., Hudry, E., Dhenain, M., Varin, J., Bièche, I., Marquer, C., Chali, F., Ayciriex, S., Auzeil, N., et al. (2015) · Brain · doi:10.1093/brain/awv166 · Cited by 223 · see citing works
Brkic, M., Balusu, S., Libert, C., & Vandenbroucke, R. E. (2015) · Mediators of Inflammation · doi:10.1155/2015/620581 · Cited by 205 · see citing works
Increased Accumulation of Intraneuronal Amyloid β in HIV-Infected Patients
HNRC, Achim, C. L., Adame, A., Dumaop, W., Everall, I. P., & Masliah, E. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9152-8 · Cited by 205 · see citing works
Aβ Amyloid Pathology Affects the Hearts of Patients With Alzheimer’s Disease
Troncone, L., Luciani, M., Coggins, M., Wilker, E. H., Ho, C.-Y., Codispoti, K. E., Frosch, M. P., Kayed, R., & del Monte, F. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.08.073 · Cited by 204 · see citing works
Long, J. M., Ray, B., & Lahiri, D. K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.366336 · Cited by 198 · see citing works
Long, J. M., Ray, B., & Lahiri, D. K. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.518241 · Cited by 187 · see citing works
Xiao, Q., Gil, S.-C., Yan, P., Wang, Y., Han, S., Gonzales, E., Perez, R., Cirrito, J. R., & Lee, J.-M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.338376 · Cited by 166 · see citing works
Hung, C. O. Y., & Livesey, F. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.095 · Cited by 159 · see citing works
Rodríguez-Rodríguez, C., Telpoukhovskaia, M., & Orvig, C. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.03.008 · Cited by 151 · see citing works
The endosomal-lysosomal pathway is dysregulated by APOE4 expression in vivo
Nuriel, T., Peng, K. Y., Ashok, A., Dillman, A. A., Figueroa, H. Y., Apuzzo, J., Ambat, J., Levy, E., Cookson, M. R., Mathews, P. M., et al. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00702 · Cited by 140 · see citing works
Venkataramani, V., Rossner, C., Iffland, L., Schweyer, S., Tamboli, I. Y., Walter, J., Wirths, O., & Bayer, T. A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.057836 · Cited by 133 · see citing works
Microglial priming in Alzheimer’s disease
Li, J.-W., Zong, Y., Cao, X.-P., Tan, L., & Tan, L. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.22 · Cited by 122 · see citing works
Contributions of DNA Damage to Alzheimer’s Disease
Lin, X., Kapoor, A., Gu, Y., Chow, M. J., Peng, J., Zhao, K., & Tang, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051666 · Cited by 117 · see citing works
“γ-secretase with mutant presenilin 1 or presenilin 2 subunit favors Aβ1-42 production [16,17].”
BackgroundShinohara, M., Fujioka, S., Murray, M. E., Wojtas, A., Baker, M., Rovelet-Lecrux, A., Rademakers, R., Das, P., Parisi, J. E., Graff-Radford, N. R., et al. (2014) · Brain · doi:10.1093/brain/awu046 · Cited by 115 · see citing works
Aubry, S., Shin, W., Crary, J. F., Lefort, R., Qureshi, Y. H., Lefebvre, C., Califano, A., & Shelanski, M. L. (2015) · PLOS ONE · doi:10.1371/journal.pone.0120352 · Cited by 106 · see citing works
APP Function and Lipids: A Bidirectional Link
Grimm, M. O. W., Mett, J., Grimm, H. S., & Hartmann, T. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00063 · Cited by 104 · see citing works
Proteomic identification of sorting nexin 6 as a negative regulator of BACE1‐mediated APP processing
Okada, H., Zhang, W., Peterhoff, C., Hwang, J. C., Nixon, R. A., Ryu, S. H., & Kim, T. (2010) · The FASEB Journal · doi:10.1096/fj.09-146357 · Cited by 102 · see citing works
Axonal transport of APP and the spatial regulation of APP cleavage and function in neuronal cells
Brunholz, S., Sisodia, S., Lorenzo, A., Deyts, C., Kins, S., & Morfini, G. (2012) · Experimental Brain Research · doi:10.1007/s00221-011-2870-1 · Cited by 92 · see citing works
Grant, J. L., Ghosn, E. E. B., Axtell, R. C., Herges, K., Kuipers, H. F., Woodling, N. S., Andreasson, K., Herzenberg, L. A., Herzenberg, L. A., & Steinman, L. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004145 · Cited by 92 · see citing works
“Scien ically altered due to the up-regulation of Ab42 during injury, inflammation, and stress in the brain (15, 16).”
BackgroundCai, W., Li, L., Sang, S., Pan, X., & Zhong, C. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-022-00985-9 · Cited by 83 · see citing works
NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models
Yang, C., Cai, C.-Z., Song, J.-X., Tan, J.-Q., Durairajan, S. S. K., Iyaswamy, A., Wu, M.-Y., Chen, L.-L., Yue, Z., Li, M., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1379633 · Cited by 83 · see citing works
Hickman, S. E., Allison, E. K., Coleman, U., Kingery-Gallagher, N. D., & El Khoury, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02780 · Cited by 80 · see citing works
Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models
Wirths, O., & Zampar, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218144 · Cited by 75 · see citing works
“Full-length Aβ peptides consisting of 40 (Aβ1–40) or 42 (Aβ1–42) amino acids, as well as the remaining APP intracellular domains (AICD) are formed in this way [6].”
BackgroundPICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4
Narayan, P., Sienski, G., Bonner, J. M., Lin, Y.-T., Seo, J., Baru, V., Haque, A., Milo, B., Akay, L. A., Graziosi, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108224 · Cited by 75 · see citing works
Rogers, K., Felsenstein, K. M., Hrdlicka, L., Tu, Z., Albayya, F., Lee, W., Hopp, S., Miller, M.-J., Spaulding, D., Yang, Z., et al. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-61 · Cited by 75 · see citing works
Huang, T. Y., Zhao, Y., Li, X., Wang, X., Tseng, I.-C., Thompson, R., Tu, S., Willnow, T. E., Zhang, Y.-W., & Xu, H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.0206-16.2016 · Cited by 69 · see citing works
Ocular manifestations of Alzheimer's disease in animal models
Parnell, M., Guo, L., Abdi, M., & Cordeiro, M. F. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/786494 · Cited by 56 · see citing works
HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective
Chu, Q., Diedrich, J. K., Vaughan, J. M., Donaldson, C. J., Nunn, M. F., Lee, K.-F., & Saghatelian, A. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b03463 · Cited by 46 · see citing works
Darmellah, A., Rayah, A., Auger, R., Cuif, M.-H., Prigent, M., Arpin, M., Alcover, A., Delarasse, C., & Kanellopoulos, J. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.400010 · Cited by 38 · see citing works
Tan, J. Z. A., Fourriere, L., Wang, J., Perez, F., Boncompain, G., & Gleeson, P. A. (2020) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-09-0487 · Cited by 37 · see citing works
Ding, X.-W., Li, R., Geetha, T., Tao, Y.-X., & Babu, J. R. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165858 · Cited by 36 · see citing works
DYRK1A Regulates the Bidirectional Axonal Transport of APP in Human-Derived Neurons
Fernandez Bessone, I., Navarro, J., Martinez, E., Karmirian, K., Holubiec, M., Alloatti, M., Goto-Silva, L., Arnaiz Yepez, C., Martins-de-Souza, D., Minardi Nascimento, J., et al. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.2551-21.2022 · Cited by 21 · see citing works
- Authors
- Thinakaran, G., & Koo, E. H.
- Affiliations
- University of Chicago (US)
- University of California San Diego (US)
- Corresponding author
- Thinakaran, Gopal
- Koo, Edward H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 283
- Issue
- 44
- Pages
- 29615-29619
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2573065
- OpenAlex
- W1968900405
- Cited by
- 1,141
- References
- 3
- Citations by year
- 2026: 40 · 2025: 44 · 2024: 49 · 2023: 43 · 2022: 43 · 2021: 65 · 2020: 73 · 2019: 70 · 2018: 68 · 2017: 60 · 2016: 78 · 2015: 82 · 2014: 74 · 2013: 66 · 2012: 85
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG019070, AG032179, AG 12376, R01AG012376, AG019070, R01AG032179, R01AG021495, AG021495)
- 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 › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid precursor protein, APP trafficking, APP proteolytic processing, amyloid-beta, Alzheimer's disease, amyloid hypothesis, secretases, amyloid plaques
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Amino Acids, Amyloid, Animals, Biological Transport, Brain, Cell Adhesion, Endocytosis, Humans, Models, Biological, Molecular Sequence Data, Protein Structure, Tertiary, Protein Transport, Amyloid Precursor Protein Secretases
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
