Reduction of the expression of the late-onset Alzheimer’s disease (AD) risk-factor BIN1 does not affect amyloid pathology in an AD mouse model
Open accessAbstract
Alzheimer's disease (AD) is pathologically characterized by the deposition of the β-amyloid (Aβ) peptide in senile plaques in the brain, leading to neuronal dysfunction and eventual decline in cognitive function. Genome-wide association studies have identified the bridging integrator 1 ( BIN1 ) gene within the second most significant susceptibility locus for late-onset AD. BIN1 is a member of the amphiphysin family of proteins and has reported roles in the generation of membrane curvature and endocytosis. Endocytic dysfunction is a pathological feature of AD, and endocytosis of the amyloid precursor protein is an important step in its subsequent cleavage by β-secretase (BACE1). In vitro evidence implicates BIN1 in endosomal sorting of BACE1 and Aβ generation in neurons, but a role for BIN1 in this process in vivo is yet to be described. Here, using biochemical and immunohistochemistry analyses we report that a 50% global reduction of BIN1 protein levels resulting from a single Bin1 allele deletion in mice does not change BACE1 levels or localization in vivo , nor does this reduction alter the production of endogenous murine Aβ in nontransgenic mice. Furthermore, we found that reduction of BIN1 levels in the 5XFAD mouse model of amyloidosis does not alter Aβ deposition nor behavioral deficits associated with cerebral amyloid burden. Finally, a conditional BIN1 knockout in excitatory neurons did not alter BACE1, APP, C-terminal fragments derived from BACE1 cleavage of APP, or endogenous Aβ levels. These results indicate that BIN1 function does not regulate Aβ generation in vivo .
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Deleting a single BIN1 or CD2AP allele did not modify amyloid deposition in mouse models of AD.
“However, despite these effects on Aβ production in vitro, deleting a single BIN1 or CD2AP allele did not modify amyloid deposition in mouse models of AD [2, 87].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [2]
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Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · see citing works
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · cited 1× · see citing works
“The role of BIN1 in the brain remains largely unknown, but several lines of evidence indicate its expression in a range of brain cell subtypes (11, 12, 28).”
BackgroundNaj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Lee, S., Viqar, F., Zimmerman, M. E., Narkhede, A., Tosto, G., Benzinger, T. L. S., Marcus, D. S., Fagan, A. M., Goate, A., Fox, N. C., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24647 · Cited by 542 · see citing works
Aβ reduction in BACE1 heterozygous null 5XFAD mice is associated with transgenic APP level
Sadleir, K. R., Eimer, W. A., Cole, S. L., & Vassar, R. (2015) · Molecular Neurodegeneration · doi:10.1186/1750-1326-10-1 · Cited by 213 · see citing works
De Rossi, P., Buggia-Prévot, V., Clayton, B. L. L., Vasquez, J. B., van Sanford, C., Andrew, R. J., Lesnick, R., Botté, A., Deyts, C., Salem, S., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0124-1 · Cited by 151 · cited 2× · see citing works
“The role of BIN1 in the brain remains largely unknown, but several lines of evidence indicate its expression in a range of brain cell subtypes (11, 12, 28).”
BackgroundSelf-citationDodson, S. E., Andersen, O. M., Karmali, V., Fritz, J. J., Cheng, D., Peng, J., Levey, A. I., Willnow, T. E., & Lah, J. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4582-08.2008 · Cited by 141 · see citing works
Tampellini, D., Rahman, N., Gallo, E. F., Huang, Z., Dumont, M., Capetillo-Zarate, E., Ma, T., Zheng, R., Lu, B., Nanus, D. M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2292-09.2009 · Cited by 127 · see citing works
BIN1 regulates BACE1 intracellular trafficking and amyloid-β production
Miyagawa, T., Ebinuma, I., Morohashi, Y., Hori, Y., Young Chang, M., Hattori, H., Maehara, T., Yokoshima, S., Fukuyama, T., Tsuji, S., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw146 · Cited by 95 · cited 3× · see citing works
“The loss of Bin1 expression was shown in one study to increase BACE1 levels and A production in neurons, with the subsequent analysis in immortalized cells lines implicating loss of endosomal trafficking and lysosomal degradation of BACE1 as the cause (26).”
BackgroundResultOu-Yang, M.-H., & Van Nostrand, W. E. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-134 · Cited by 30 · see citing works
Flagged first, then by citations
Research works printed but not linked: 45
- Musiek, E. S., and Holtzman, D. M. (2015) Three dimensions of the amy- loid hypothesis: Time, space and "wingmen." Nat. Neurosci. 18, 800 -806 CrossRef Medline · DOI
- Seshadri, S., Fitzpatrick, A. L., Ikram, M. A., DeStefano, A. L., Gudnason, V., Boada, M., Bis, J. C., Smith, A. V., Carassquillo, M. M., Lambert, J. C., Harold, D., Schrijvers, E. M., Ramirez-Lorca, R., Debette, S., Longstreth, W. T., Jr., et al. (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303, 1832-1840 CrossRef Medline BIN1 does not alter -amyloid pathology in vivo 5. Prokic, I., Cowling, B. S., and Laporte, J. (2014) Amphiphysin 2 (BIN1) in physiology and diseases. J. Mol. Med. 92, 453-463 CrossRef Medline · DOI · Paper page
- Leprince, C., Romero, F., Cussac, D., Vayssiere, B., Berger, R., Tavitian, A., and Camonis, J. H. (1997) A new member of the amphiphysin family connecting endocytosis and signal transduction pathways. J. Biol. Chem. 272, 15101-15105 CrossRef Medline · DOI · Paper page
- Tan, M.-S., Yu, J.-T., and Tan, L. (2013) Bridging integrator 1 (BIN1): Form, function, and Alzheimer's disease. Trends Mol. Med. 19, 594 -603 CrossRef Medline · DOI
- Wigge, P., and McMahon, H. T. (1998) The amphiphysin family of pro- teins and their role in endocytosis at the synapse. Trends Neurosci. 21, 339 -344 CrossRef Medline · DOI · Paper page
- Glennon, E. B., Whitehouse, I. J., Miners, J. S., Kehoe, P. G., Love, S., Kellett, K. A., and Hooper, N. M. (2013) BIN1 is decreased in sporadic but not familial Alzheimer's disease or in aging. PLoS One 8, e78806 CrossRef Medline · DOI · Paper page
- Holler, C. J., Davis, P. R., Beckett, T. L., Platt, T. L., Webb, R. L., Head, E., and Murphy, M. P. (2014) Bridging integrator 1 (BIN1) protein expression increases in the Alzheimer's disease brain and correlates with neurofibril- lary tangle pathology. J. Alzheimer's Dis. 42, 1221-1227 CrossRef Medline · DOI · Paper page
- Adams, S. L., Tilton, K., Kozubek, J. A., Seshadri, S., and Delalle, I. (2016) Subcellular changes in bridging integrator 1 protein expression in the cerebral cortex during the progression of Alzheimer disease pathology. J. Neuropathol Exp. Neurol. 75, 779 -790 CrossRef Medline · DOI · Paper page
- Chapuis, J., Hansmannel, F., Gistelinck, M., Mounier, A., Van Cauwenber- ghe, C., Kolen, K. V., Geller, F., Sottejeau, Y., Harold, D., Dourlen, P., Grenier-Boley, B., Kamatani, Y., Delepine, B., Demiautte, F., Zelenika, D., et al. (2013) Increased expression of BIN1 mediates Alzheimer genetic risk by modulating tau pathology. Mol. Psychiatry 18, 1225-1234 CrossRef Medline · DOI · Paper page
- De Rossi, P., Buggia-Prevot, V., Andrew, R., Krause, S., Woo, E., Nelson, P., Pytel, P., and Thinakaran, G. (2017) BIN1 localization is distinct from Tau tangles in Alzheimer's disease. Matters CrossRef Medline · DOI
- De Rossi, P., Andrew, R. J., Musial, T. F., Buggia-Prevot, V., Xu, G., Pon- nusamy, M., Ly, H., Krause, S. V., Rice, R. C., de l'Estoile, V., Valin, T., Salem, S., Despa, F., Borchelt, D. R., Bindokas, V. P., Nicholson, D. A., and Thinakaran, G. (2018) Aberrant accrual of BIN1 near Alzheimer's disease amyloid deposits in transgenic models. Brain Pathol. CrossRef Medline · DOI
- Karch, C. M., Jeng, A. T., Nowotny, P., Cady, J., Cruchaga, C., and Goate, A. M. (2012) Expression of novel Alzheimer's disease risk genes in control and Alzheimer's disease brains. PLoS One 7, e50976 CrossRef Medline · DOI · Paper page
- Cataldo, A. M., Peterhoff, C. M., Troncoso, J. C., Gomez-Isla, T., Hyman, B. T., and Nixon, R. A. (2000) Endocytic pathway abnormalities precede amyloid  deposition in sporadic Alzheimer's disease and Down syn- drome. Am. J. Pathol. 157, 277-286 CrossRef Medline · DOI
- Thinakaran, G., and Koo, E. H. (2008) Amyloid precursor protein traffick- ing, processing, and function. J. Biol. Chem. 283, 29615-29619 CrossRef Medline · DOI · Paper page
- Rajendran, L., and Annaert, W. (2012) Membrane trafficking pathways in Alzheimer's disease. Traffic 13, 759 -770 CrossRef Medline · DOI
- Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., et al. (1999) Beta-secretase cleavage of Alz- heimer's amyloid precursor protein by the transmembrane aspartic pro- tease BACE. Science 286, 735-741 CrossRef Medline · DOI · Paper page
- Buggia-Prévot, V., Fernandez, C. G., Udayar, V., Vetrivel, K. S., Elie, A., Roseman, J., Sasse, V. A., Lefkow, M., Meckler, X., Bhattacharyya, S., George, M., Kar, S., Bindokas, V. P., Parent, A. T., Rajendran, L., Band, H., Vassar, R., and Thinakaran, G. (2013) A function for EHD family proteins in unidirectional retrograde dendritic transport of BACE1 and Alzhei- mer's disease A production. Cell Rep. 5, 1552-1563 CrossRef Medline · DOI · Paper page
- Buggia-Prévot, V., Fernandez, C. G., Riordan, S., Vetrivel, K. S., Roseman, J., Waters, J., Bindokas, V. P., Vassar, R., and Thinakaran, G. (2014) Axonal BACE1 dynamics and targeting in hippocampal neurons: A role for Rab11 GTPase. Mol. Neurodegener. 9, 1 CrossRef Medline · DOI
- Das, U., Scott, D. A., Ganguly, A., Koo, E. H., Tang, Y., and Roy, S. (2013) Activity-induced convergence of APP and BACE-1 in acidic microdo- mains via an endocytosis-dependent pathway. Neuron 79, 447-460 CrossRef Medline · DOI
- Ubelmann, F., Burrinha, T., Salavessa, L., Gomes, R., Ferreira, C., Moreno, N., and Guimas Almeida, C. (2017) Bin1 and CD2AP polarise the endo- cytic generation of beta-amyloid. EMBO Rep. 18, 102-122 CrossRef Medline · DOI · Paper page
- Veeraraghavalu, K., Zhang, C., Zhang, X., Tanzi, R. E., and Sisodia, S. S. (2014) Age-dependent, non-cell-autonomous deposition of amyloid from synthesis of beta-amyloid by cells other than excitatory neurons. J. Neu- rosci. 34, 3668 -3673 CrossRef Medline · DOI
- Muller, A. J., Baker, J. F., DuHadaway, J. B., Ge, K., Farmer, G., Donover, P. S., Meade, R., Reid, C., Grzanna, R., Roach, A. H., Shah, N., Soler, A. P., and Prendergast, G. C. (2003) Targeted disruption of the murine Bin1/ amphiphysin II gene does not disable endocytosis but results in embryonic cardiomyopathy with aberrant myofibril formation. Mol. Cell Biol. 23, 4295-4306 CrossRef Medline · DOI · Paper page
- Rempe, D., Vangeison, G., Hamilton, J., Li, Y., Jepson, M., and Federoff, H. J. (2006) Synapsin I Cre transgene expression in male mice produces germline recombination in progeny. Genesis 44, 44 -49 CrossRef Medline · DOI
- Hitt, B., Riordan, S. M., Kukreja, L., Eimer, W. A., Rajapaksha, T. W., and Vassar, R. (2012) -Site amyloid precursor protein (APP)-cleaving en- zyme 1 (BACE1)-deficient mice exhibit a close homolog of L1 (CHL1) loss-of-function phenotype involving axon guidance defects. J. Biol. Chem. 287, 38408 -38425 CrossRef Medline · DOI
- Cirrito, J. R., Kang, J. E., Lee, J., Stewart, F. R., Verges, D. K., Silverio, L. M., Bu, G., Mennerick, S., and Holtzman, D. M. (2008) Endocytosis is required for synaptic activity-dependent release of amyloid- in vivo. Neuron 58, 42-51 CrossRef Medline · DOI · Paper page
- Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., and Holtzman, D. M. (2005) Synaptic activity regulates interstitial fluid amyloid- levels in vivo. Neuron 48, 913-922 CrossRef Medline · DOI · Paper page
- Wang, P., Yang, G., Mosier, D. R., Chang, P., Zaidi, T., Gong, Y. D., Zhao, N. M., Dominguez, B., Lee, K. F., Gan, W. B., and Zheng, H. (2005) Defec- tive neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-like protein 2. J. Neurosci. 25, 1219 -1225 CrossRef Medline BIN1 does not alter -amyloid pathology in vivo 38. Wilhelm, B. G., Mandad, S., Truckenbrodt, S., Kröhnert, K., Schäfer, C., Rammner, B., Koo, S. J., Classen, G. A., Krauss, M., Haucke, V., Urlaub, H., and Rizzoli, S. O. (2014) Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344, 1023-1028 CrossRef Medline · DOI · Paper page
- Shi, Y., and Holtzman, D. M. (2018) Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat. Rev. Immunol. 18, 759 -772 CrossRef Medline · DOI · Paper page
- Calafate, S., Flavin, W., Verstreken, P., and Moechars, D. (2016) Loss of Bin1 promotes the propagation of Tau pathology. Cell Rep. 17, 931-940 CrossRef Medline · DOI · Paper page
- Malki, I., Cantrelle, F. X., Sottejeau, Y., Lippens, G., Lambert, J. C., and Landrieu, I. (2017) Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau proteins-role of the SH3 domain. FEBS J. 284, 3218 -3229 CrossRef Medline · DOI · Paper page
- Kanatsu, K., Morohashi, Y., Suzuki, M., Kuroda, H., Watanabe, T., Tomita, T., and Iwatsubo, T. (2014) Decreased CALM expression reduces A42 to total A ratio through clathrin-mediated endocytosis of ␥-secretase. Nat. Commun. 5, 3386 CrossRef Medline · DOI
- Andersen, O. M., Rudolph, I. M., and Willnow, T. E. (2016) Risk factor SORL1: From genetic association to functional validation in Alzheimer's disease. Acta Neuropathol. 132, 653-665 CrossRef Medline · DOI
- Andersen, O. M., Reiche, J., Schmidt, V., Gotthardt, M., Spoelgen, R., Behlke, J., von Arnim, C. A., Breiderhoff, T., Jansen, P., Wu, X., Bales, K. R., Cappai, R., Masters, C. L., Gliemann, J., Mufson, E. J., Hyman, B. T., Paul, S. M., Nykjaer, A., and Willnow, T. E. (2005) Neuronal sorting protein- related receptor sorLA/LR11 regulates processing of the amyloid precur- sor protein. Proc. Natl. Acad. Sci. U.S.A. 102, 13461-13466 CrossRef Medline · DOI · Paper page
- Rohe, M., Carlo, A. S., Breyhan, H., Sporbert, A., Militz, D., Schmidt, V., Wozny, C., Harmeier, A., Erdmann, B., Bales, K. R., Wolf, S., Kemper- mann, G., Paul, S. M., Schmitz, D., Bayer, T. A., Willnow, T. E., and An- dersen, O. M. (2008) Sortilin-related receptor with A-type repeats (SORLA) affects the amyloid precursor protein-dependent stimulation of ERK signaling and adult neurogenesis. J. Biol. Chem. 283, 14826 -14834 CrossRef Medline · DOI
- Dugas, J. C., Tai, Y. C., Speed, T. P., Ngai, J., and Barres, B. A. (2006) Functional genomic analysis of oligodendrocyte differentiation. J. Neuro- sci. 26, 10967-10983 CrossRef Medline · DOI · Paper page
- Nasrabady, S. E., Rizvi, B., Goldman, J. E., and Brickman, A. M. (2018) White matter changes in Alzheimer's disease: A focus on myelin and oligodendrocytes. Acta Neuropathol. Commun. 6, 22 CrossRef Medline · DOI · Paper page
- Sadleir, K. R., Kandalepas, P. C., Buggia-Prevot, V., Nicholson, D. A., Thi- nakaran, G., and Vassar, R. (2016) Presynaptic dystrophic neurites sur- rounding amyloid plaques are sites of microtubule disruption, BACE1 elevation, and increased A generation in Alzheimer's disease. Acta. Neu- ropathol. 132, 235-256 CrossRef Medline · DOI · Paper page
- Gu, L., Wu, D., Tang, X., Qi, X., Li, X., Bai, F., Chen, X., Ren, Q., and Zhang, Z. (2018) Myelin changes at the early stage of 5XFAD mice. Brain Res. Bull. 137, 285-293 CrossRef Medline · DOI · Paper page
- Chang, M. Y., Boulden, J., Katz, J. B., Wang, L., Meyer, T. J., Soler, A. P., Muller, A. J., and Prendergast, G. C. (2007) Bin1 ablation increases sus- ceptibility to cancer during aging, particularly lung cancer. Cancer Res. 67, 7605-7612 CrossRef Medline · DOI
- Cheng, H., Vetrivel, K. S., Drisdel, R. C., Meckler, X., Gong, P., Leem, J. Y., Li, T., Carter, M., Chen, Y., Nguyen, P., Iwatsubo, T., Tomita, T., Wong, P. C., Green, W. N., Kounnas, M. Z., and Thinakaran, G. (2009) S-palmi- toylation of ␥-secretase subunits nicastrin and APH-1. J. Biol. Chem. 284, 1373-1384 CrossRef Medline · DOI
- Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordstedt, C., Seeger, M., Hardy, J., Levey, A. I., Gandy, S. E., Jenkins, N. A., Copeland, N. G., Price, D. L., and Sisodia, S. S. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190 CrossRef Medline · DOI
- De Rossi, P., Harde, E., Dupuis, J. P., Martin, L., Chounlamountri, N., Bardin, M., Watrin, C., Benetollo, C., Pernet-Gallay, K., Luhmann, H. J., Honnorat, J., Malleret, G., Groc, L., Acker-Palmer, A., Salin, P. A., and Meissirel, C. (2016) A critical role for VEGF and VEGFR2 in NMDA receptor synaptic function and fear-related behavior. Mol. Psychiatry 21, 1768 -1780 CrossRef Medline · DOI
- Gong, P., Roseman, J., Fernandez, C. G., Vetrivel, K. S., Bindokas, V. P., Zitzow, L. A., Kar, S., Parent, A. T., and Thinakaran, G. (2011) Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice. Mol. Neurodegener. 6, 87 CrossRef Medline · DOI
- Andrew, R. J., Fernandez, C. G., Stanley, M., Jiang, H., Nguyen, P., Rice, R. C., Buggia-Prévot, V., De Rossi, P., Vetrivel, K. S., Lamb, R., Argemi, A., Allaert, E. S., Rathbun, E. M., Krause, S. V., Wagner, S. L., Parent, A. T., Holtzman, D. M., and Thinakaran, G. (2017) Lack of BACE1 S-palmitoy- lation reduces amyloid burden and mitigates memory deficits in trans- genic mouse models of Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 114, E9665-E9674 CrossRef Medline · DOI
- Giannoni, P., Gaven, F., de Bundel, D., Baranger, K., Marchetti-Gauthier, E., Roman, F. S., Valjent, E., Marin, P., Bockaert, J., Rivera, S., and Claeysen, S. (2013) Early administration of RS 67333, a specific 5-HT4 receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of Alzheimer's disease. Front. Aging Neurosci. 5, 96 CrossRef Medline BIN1 does not alter -amyloid pathology in vivo · DOI
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- Authors
- Andrew, R. J., De Rossi, P., Nguyen, P., Kowalski, H. R., Recupero, A. J., Guerbette, T., Krause, S. V., Rice, R. C., Laury-Kleintop, L., Wagner, S. L., & Thinakaran, G.
- Affiliations
- University of Chicago (US)
- University of California San Diego (US)
- Corresponding author
- Thinakaran, Gopal
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 294
- Issue
- 12
- Pages
- 4477-4487
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC6433054
- OpenAlex
- W2914475876
- Cited by
- 55
- References
- 11
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 23 · 2021: 4 · 2020: 6 · 2019: 4
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute on Aging (AG054223, AG056061)
- Cure Alzheimer's Fund (16477)
- Alzheimer's Association (AARF-17–501228)
- Illinois Department of Public Health (83282004F)
- BrightFocus Foundation (A2017366F)
- HHS | National Institutes of Health (S10OD010649)
- 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
- BIN1, late-onset Alzheimer's disease, amyloid-beta, BACE1, amyloid precursor protein, endocytosis, 5xFAD mice, conditional knockout, excitatory neurons, amyloid plaques, genetic susceptibility, APP C-terminal fragments
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Endocytosis, Female, Humans, Male, Nerve Tissue Proteins, Endosomes, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Mice, Knockout, Genetic Predisposition to Disease, Tumor Suppressor Proteins, Adaptor Proteins, Signal Transducing, Mice, Amyloid Precursor Protein Secretases
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