Initial assessment of the spatial learning, reversal, and sequencing task capabilities of knock-in rats with humanizing mutations in the Aβ-coding region of App
Open accessPublished version of a preprint
Abstract
Model organisms mimicking the pathogenesis of human diseases are useful for identifying pathogenic mechanisms and testing therapeutic efficacy of compounds targeting them. Models of Alzheimer’s disease (AD) and related dementias (ADRD) aim to reproduce the brain pathology associated with these neurodegenerative disorders. Transgenic models, which involve random insertion of disease-causing genes under the control of artificial promoters, are efficient means of doing so. There are confounding factors associated with transgenic approaches, however, including target gene overexpression, dysregulation of endogenous gene expression at transgenes’ integration sites, and limitations in mimicking loss-of-function mechanisms. Furthermore, the choice of species is important, and there are anatomical, physiological, and cognitive reasons for favoring the rat over the mouse, which has been the standard for models of neurodegeneration and dementia. We report an initial assessment of the spatial learning, reversal, and sequencing task capabilities of knock-in (KI) Long-Evans rats with humanizing mutations in the Aβ-coding region of App , which encodes amyloid precursor protein ( App h/h rats), using the IntelliCage, an automated operant social home cage system, at 6–8 weeks of age, then again at 4–5 months of age. These rats were previously generated as control organisms for studies on neurodegeneration involving other knock-in rat models from our lab. App h/h rats of either sex can acquire place learning and reversal tasks. They can also acquire a diagonal sequencing task by 6–8 weeks of age, but not a more advanced serial reversal task involving alternating diagonals, even by 4–5 months of age. Thus, longitudinal behavioral analysis with the IntelliCage system can be useful to determine, in follow-up studies, whether KI rat models of Familial AD (FAD), sporadic late onset AD (LOAD), and of ADRD develop aging-dependent learning and memory deficits.
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The Apph allele enables the physiological production of human Aβ instead of rodent Aβ from the endogenous rat App gene.
“The Apph allele enables the physiological production of human Aβ instead of rodent Aβ from the endogenous rat App gene [43–49].”
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Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · see citing works
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676 · see citing works
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Molecular Architecture of the Mouse Nervous System
Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L. E., La Manno, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.021 · Cited by 2,995 · see citing works
Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · see citing works
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · see citing works
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline
Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., et al. (2012) · Nature · doi:10.1038/nature11283 · Cited by 1,738 · see citing works
Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., & Lannfelt, L. (1992) · Nature Genetics · doi:10.1038/ng0892-345 · Cited by 1,513 · see citing works
Katzman, R., Terry, R., DeTeresa, R., Brown, T., Davies, P., Fuld, P., Renbing, X., & Peck, A. (1988) · Annals of Neurology · doi:10.1002/ana.410230206 · Cited by 1,225 · see citing works
Frequent amyloid deposition without significant cognitive impairment among the elderly
Aizenstein, H. J., Nebes, R. D., Saxton, J. A., Price, J. C., Mathis, C. A., Tsopelas, N. D., Ziolko, S. K., James, J. A., Snitz, B. E., Houck, P. R., et al. (2008) · Archives of Neurology · doi:10.1001/archneur.65.11.1509 · Cited by 1,059 · see citing works
Mutation-Specific Functional Impairments in Distinct Tau Isoforms of Hereditary FTDP-17
Hong, M. (1998) · Science · doi:10.1126/science.282.5395.1914 · Cited by 1,003 · see citing works
Structures of filaments from Pick’s disease reveal a novel tau protein fold
Falcon, B., Zhang, W., Murzin, A. G., Murshudov, G. N., Garringer, H. J., Vidal, R., Crowther, R. A., Ghetti, B. F., Scheres, S. H. W., & Goedert, M. (2018) · Nature · doi:10.1038/s41586-018-0454-y · Cited by 837 · see citing works
Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease
Villemagne, V. L., Pike, K. E., Chételat, G., Ellis, K. A., Mulligan, R. S., Bourgeat, P., Ackermann, U., Jones, G., Szoeke, C., Salvado, O., et al. (2011) · Annals of Neurology · doi:10.1002/ana.22248 · Cited by 833 · see citing works
Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810 · see citing works
Neural correlates, computation and behavioural impact of decision confidence
Kepecs, A., Uchida, N., Zariwala, H. A., & Mainen, Z. F. (2008) · Nature · doi:10.1038/nature07200 · Cited by 809 · see citing works
Tau protein pathology in neurodegenerative diseases
Spillantini, M. G., & Goedert, M. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01337-x · Cited by 683 · see citing works
Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease
Killiany, R., Gómez‐Isla, T., Moss, M. B., Kikinis, R., Sándor, T., Jolesz, F. A., Tanzi, R. E., Jones, K. J., Hyman, B. T., & Albert, M. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200004)47:4 · Cited by 659 · see citing works
Identification of normal and pathological aging in prospectively studied nondemented elderly humans
Dickson, D. W., Crystal, H. A., Mattiace, L. A., Masur, D. M., Blau, A. D., Davies, P., Yen, S.-H., & Aronson, M. K. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90027-u · Cited by 643 · see citing works
Lanoiselée, H.-M., Nicolas, G., Wallon, D., Rovelet-Lecrux, A., Lacour, M., Rousseau, S., Richard, A.-C., Pasquier, F., Rollin-Sillaire, A., Martinaud, O., et al. (2017) · PLOS Medicine · doi:10.1371/journal.pmed.1002270 · Cited by 616 · see citing works
Differences Between Women and Men in Incidence Rates of Dementia and Alzheimer’s Disease
Beam, C. R., Kaneshiro, C., Jang, J. Y., Reynolds, C. A., Pedersen, N. L., & Gatz, M. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-180141 · Cited by 550 · see citing works
The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind
Ricciarelli, R., & Fedele, E. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170116143743 · Cited by 380 · see citing works
Andreadis, A. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.08.010 · Cited by 311 · see citing works
Steinbeck, J. A., Choi, S. J., Mrejeru, A., Ganat, Y. M., Deisseroth, K. A., Sulzer, D. L., Mosharov, E. V., & Studer, L. (2015) · Nature Biotechnology · doi:10.1038/nbt.3124 · Cited by 300 · see citing works
Foote, A. L., & Crystal, J. D. (2007) · Current Biology · doi:10.1016/j.cub.2007.01.061 · Cited by 272 · see citing works
Tau Mutations Cause Frontotemporal Dementias
Goedert, M., Crowther, R. A., & Spillantini, M. G. (1998) · Neuron · doi:10.1016/s0896-6273(00)80615-7 · Cited by 268 · see citing works
The touchscreen cognitive testing method for rodents: How to get the best out of your rat
Bussey, T. J., Padain, T. L., Skillings, E. A., Winters, B. D., Morton, A. J., & Saksida, L. M. (2008) · Learning & Memory · doi:10.1101/lm.987808 · Cited by 255 · see citing works
Cognitive deficits in single App knock-in mouse models
Masuda, A., Kobayashi, Y., Kogo, N., Saito, T., Saido, T. C., & Itohara, S. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.07.001 · Cited by 248 · see citing works
Housing, husbandry and handling of rodents for behavioral experiments
Deacon, R. M. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.120 · Cited by 246 · see citing works
Delaère, P., Duyckaerts, C., Masters, C., Beyreuther, K., Piette, F., & Hauw, J.-J. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90391-l · Cited by 186 · see citing works
Tau isoform regulation is region‐ and cell‐specific in mouse brain
McMillan, P., Korvatska, E., Poorkaj, P., Evstafjeva, Z., Robinson, L., Greenup, L., Leverenz, J., Schellenberg, G. D., & D'Souza, I. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21867 · Cited by 179 · see citing works
Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?
Panza, F., Lozupone, M., Seripa, D., & Imbimbo, B. P. (2019) · Annals of Neurology · doi:10.1002/ana.25410 · Cited by 178 · see citing works
Campbell, M. G., Veesler, D., Cheng, A., Potter, C. S., & Carragher, B. O. (2015) · eLife · doi:10.7554/elife.06380 · Cited by 163 · see citing works
Tamayev, R., Matsuda, S., Arancio, O., & D'Adamio, L. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100195 · Cited by 142 · see citing works
Self-citationIntelliCage as a tool for measuring mouse behavior – 20 years perspective
Kiryk, A., Janusz, A. K., Zglinicki, B., Turkes, E., Knapska, E., Konopka, W., Lipp, H.-P., & Kaczmarek, L. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112620 · Cited by 126 · see citing works
Mutations in the tau gene that cause an increase in three repeat tau and frontotemporal dementia
Stanford, P. M. (2003) · Brain · doi:10.1093/brain/awg090 · Cited by 125 · see citing works
Automated test of behavioral flexibility in mice using a behavioral sequencing task in IntelliCage
Endo, T., Maekawa, F., Võikar, V., Haijima, A., Uemura, Y., Zhang, Y., Miyazaki, W., Suyama, S., Shimazaki, K., Wolfer, D. P., et al. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.02.037 · Cited by 119 · see citing works
Whishaw, I. Q., Metz, G. A. S., Kolb, B., & Pellis, S. M. (2001) · Developmental Psychobiology · doi:10.1002/dev.1041 · Cited by 110 · see citing works
Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies
Hanes, J., Zilka, N., Bartkova, M., Caletkova, M., Dobrota, D., & Novak, M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05869.x · Cited by 109 · see citing works
Janke, C., Beck, M., Stahl, T., Holzer, M., Brauer, K., Bigl, V., & Arendt, T. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00079-0 · Cited by 104 · see citing works
Mifflin, M. A., Winslow, W., Surendra, L., Tallino, S., Vural, A. S., & Velázquez, R. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.01.018 · Cited by 87 · see citing works
Tamayev, R., & D’Adamio, L. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-19 · Cited by 81 · see citing works
Self-citationRen, S., Yao, W., Tambini, M. D., Yin, T., Norris, K. A., & D'Adamio, L. (2020) · eLife · doi:10.7554/elife.57513 · Cited by 68 · see citing works
Self-citationTyr682 in the Intracellular Domain of APP Regulates Amyloidogenic APP Processing In Vivo
Barbagallo, A., Weldon, R., Tamayev, R., Zhou, D., Giliberto, L., Foreman, O., & D'adamio, L. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015503 · Cited by 65 · see citing works
Self-citationA novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy
Grover, A., England, E., Baker, M., Sahara, N., Adamson, J. L., Granger, B., Houlden, H., Passant, U., Yen, S.-H. C., Deture, M. A., et al. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00393-5 · Cited by 62 · see citing works
Tamayev, R., Matsuda, S., Fà, M., Arancio, O., & D'adamio, L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011689107 · Cited by 61 · see citing works
Self-citationDevelopments in Tau PET Imaging
Zimmer, E. R., Leuzy, A., Gauthier, S., & Rosa-Neto, P. (2014) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2014.15 · Cited by 60 · see citing works
Tamayev, R., Giliberto, L., Li, W., d’Abramo, C., Arancio, O., Vidal, R., & D'adamio, L. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3917-10.2010 · Cited by 55 · see citing works
Self-citationAPP heterozygosity averts memory deficit in knockin mice expressing the Danish dementia BRI2 mutant
Tamayev, R., Matsuda, S., Giliberto, L., Arancio, O., & D'adamio, L. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.161 · Cited by 51 · see citing works
Self-citationModeling familial British and Danish dementia
Garringer, H. J., Murrell, J. R., D'adamio, L., Ghetti, B. F., & Vidal, R. (2009) · Brain Structure and Function · doi:10.1007/s00429-009-0221-9 · Cited by 48 · see citing works
Self-citationBarbagallo, A., Wang, Z., Zheng, H., & D'adamio, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.c111.219873 · Cited by 47 · see citing works
Self-citationTambini, M. D., Norris, K. A., & D'adamio, L. (2020) · eLife · doi:10.7554/elife.52612 · Cited by 47 · see citing works
Self-citationRen, S., Breuillaud, L., Yao, W., Yin, T., Norris, K. A., Zehntner, S. P., & D’Adamio, L. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.016395 · Cited by 47 · see citing works
Self-citationUrbach, Y. K., Raber, K. A., Canneva, F., et al. (2014) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2014.06.017 · Cited by 45 · see citing works
Bartelle, B. B., Barandov, A., & Jasanoff, A. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4050-15.2016 · Cited by 45 · see citing works
Testing cognitive functions in rodent disease models: Present pitfalls and future perspectives
Tanila, H. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.05.040 · Cited by 43 · see citing works
Tambini, M. D., Yao, W., & D'Adamio, L. (2019) · Aging Cell · doi:10.1111/acel.13033 · Cited by 40 · see citing works
Self-citationUeno, H., YAMAGUCHI, T. J., Fukunaga, S., Okada, Y., Yano, Y., Hoshino, M., & Matsuzaki, K. (2014) · Biochemistry · doi:10.1021/bi501239q · Cited by 38 · see citing works
Generation and Initial Characterization of FDD Knock In Mice
Giliberto, L., Matsuda, S., Vidal, R., & D'adamio, L. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007900 · Cited by 34 · see citing works
Self-citationLeuzy, A., Zimmer, E. R., Heurling, K., Rosa-Neto, P., & Gauthier, S. (2014) · Amyloid · doi:10.3109/13506129.2014.926267 · Cited by 31 · see citing works
Iman, I. N., Yusof, N. A. M., Talib, U. N., Ahmad, N. A. Z., Norazit, A., Kumar, J., Mehat, M. Z., Jayabalan, N., Muthuraju, S., Stefaniuk, M., et al. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.683780 · Cited by 31 · see citing works
Zimmer, E. R., Leuzy, A., Bhat, V., Gauthier, S., & Rosa-Neto, P. (2014) · Translational Neurodegeneration · doi:10.1186/2047-9158-3-6 · Cited by 30 · see citing works
Zehntner, S. P., Chakravarty, M. M., Bolovan, R. J., Chan, C., & Bedell, B. J. (2008) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2008.950345 · Cited by 26 · see citing works
Tambini, M. D., & D'adamio, L. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.012542 · Cited by 26 · see citing works
Self-citationBarbagallo, A., Wang, Z., Zheng, H., & D'adamio, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018006 · Cited by 24 · see citing works
Self-citationTamayev, R., & D'adamio, L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5193-11.2012 · Cited by 23 · see citing works
Self-citationOptogenetics for neurodegenerative diseases.
Vann, K. T., & Xiong, Z. (2016) · PubMed Central · Cited by 23 · see citing works
Effects of GABAB receptors in the insula on recognition memory observed with intellicage
Wu, N., Wang, F., Jin, Z., Zhang, Z., Wang, L.-K., Zhang, C., & Sun, T. (2017) · Behavioral and Brain Functions · doi:10.1186/s12993-017-0125-4 · Cited by 22 · see citing works
Tamayev, R., Akpan, N., Arancio, O., Troy, C. M., & D'adamio, L. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-60 · Cited by 21 · see citing works
Self-citationA novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17.
Kowalska, A., Hasegawa, M., Miyamoto, K., Akiguchi, I., Ikemoto, A., Takahashi, K., Araki, W., & Tabira, T. (2002) · PubMed · Cited by 20 · see citing works
Yin, T., Yao, W., Lemenze, A. D., & D’Adamio, L. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015679 · Cited by 20 · see citing works
Self-citationMasuda, A., Kobayashi, Y., & Itohara, S. (2018) · Journal of Visualized Experiments · doi:10.3791/58009 · Cited by 15 · see citing works
Tambini, M. D., & D'adamio, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-60800-1 · Cited by 15 · see citing works
Self-citationKlunk, W. E., Mathis, C. A., Price, J. C., DeKosky, S. T., Lopresti, B. J., Tsopelas, N. D., Saxton, J. A., & Nebes, R. D. (2009) · Springer eBooks · doi:10.1007/978-0-387-76420-7_6 · Cited by 14 · see citing works
Yin, T., Yao, W., Norris, K. A., & D’Adamio, L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101089 · Cited by 14 · see citing works
Self-citationCao, G., Wei, X., Li, W., et al. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.136192 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [41]Ren S, Breuillaud L, Yao W, Yin T, Norris KA, Zehntner SP, et al. TNFα reduces inhibitory transmission in young Trem2R47H Sporadic Alzheimer rats before observable Aβ and brain pathology. bioRxiv 2020.
Cited by
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Yesiltepe, M., Yin, T., Tambini, M., Bao, H., Pan, M., d’Abramo, C., Giliberto, L., Han, X., & D’Adamio, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01832-2 · Cited by 10 · see citing works
“The App h allele enables the physiological production of human Aβ instead of rodent Aβ from the endogenous rat App gene [43–49].”
BackgroundSelf-citationYesiltepe, M., Yin, T., Tambini, M. D., Breuillaud, L., Zehntner, S. P., & D’Adamio, L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1040576 · Cited by 6 · see citing works
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- Authors
- Pham, H., Yin, T., & D’Adamio, L.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2022-05-04
- Volume
- 17
- Issue
- 5
- Pages
- e0263546
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC9067689
- OpenAlex
- W4229049228
- Cited by
- 6
- References
- 77
- Citations by year
- 2024: 4 · 2022: 2
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (R01 AG073182, R01AG063407-03, 1RF1AG064821-01)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid precursor protein, Alzheimer's disease, related dementias, spatial learning, reversal learning, IntelliCage, learning and memory impairment, familial Alzheimer's disease, Long-Evans rats
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Mice, Transgenic, Mutation, Reversal Learning, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Long-Evans, Rats, Mobile Applications
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