Parental origin of transgene modulates amyloid-β plaque burden in the 5xFAD mouse model of Alzheimer’s disease
Open accessAbstract
In Alzheimer's disease (AD) research, the 5xFAD mouse model is commonly used as a heterozygote crossed with other genetic models to study AD pathology. We investigated whether the parental origin of the 5xFAD transgene affects plaque deposition. Using quantitative light-sheet microscopy, we found that paternal inheritance of the transgene led to a 2-fold higher plaque burden compared with maternal inheritance, a finding consistent across multiple 5xFAD colonies. This effect was not due to gestation in or rearing by 5xFAD females. Immunoblotting suggested that transgenic inheritance modulates transgenic protein expression, potentially due to genomic imprinting of the Thy1.2 promoter. Surprisingly, fewer than 20% of 5xFAD studies report breeding schemes, suggesting that this factor might confound previous findings. Our data highlight a significant determinant of plaque burden in 5xFAD mice and underscore the importance of reporting the parental origin of the transgene to improve scientific rigor and reproducibility in AD research.
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
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.
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?
Amyloid pathology is more accelerated and consistent in female 5xFAD mice compared with male 5xFAD mice.
“amyloid pathology is more accelerated and consistent in female 5xFAD mice compared with male 5xFAD mice (Forner et al., 2021; Sasmita et al., 2025).”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Sasmita et al., 2025
The LSM results (p. 3) report approximately twice the plaque burden in female 5xFAD mice compared with age-matched males at six months. That supports greater pathology at that age, but the passage does not establish faster progression or greater consistency in females; the temporal analysis on the same page concerns males. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLitter-matched animals were used for comparison when applicable to control for potential differences in expression levels arising from paternal versus maternal transmission of the 5xFAD transgene.
“To control for potential differences in expression levels arising from paternal versus maternal transmission of the 5xFAD transgene61, litter-matched animals were used for comparison when applicable.”
From Lymphoid gene expression supports neuroprotective microglia function (2025) · cites this paper as [61]
The parental origin of the 5xFAD transgene impacts Aβ burden in offspring.
“Recent evidence showed that the parental origin of the 5xFAD transgene impacts Aβ burden in offspring (Sasmita et al., 2025)”
From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Sasmita et al., 2025
Aβ can bind to lipoproteins such as clusterin (ApoJ) and ApoE in the brain, which facilitates its clearance by microglia via TREM2.
“However, Aβ can bind to lipoproteins such as clusterin (ApoJ) and ApoE in the brain82–84, which facilitates its clearance by microglia via TREM281.”
From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [82]
The citation is attached to the claim that lipoprotein-bound Aβ is cleared by microglia via TREM2. Our copy discusses 5xFAD plaque burden (Introduction, p. 2) and mentions Trem2 only when excluding crossbred models from a database search (Reporting of Thy1 promoter-driven transgenic AD models, p. 14). Searches for TREM2-mediated clearance and for clusterin/ApoJ and ApoE binding found no passage addressing that mechanism. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
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
Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP
Feng, G., Mellor, R. H., Bernstein, M., Keller-Peck, C., Nguyen, Q. T., Wallace, M., Nerbonne, J. M., Lichtman, J. W., & Sanes, J. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00084-2 · Cited by 3,042 · cited 1× · see citing works
“34 Our findings underscore the need to stringently monitor breeding schemes of other widely used AD mouse models using the Thy1.”
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526 · see citing works
Single App knock-in mouse models of Alzheimer’s disease
Saito, T., Matsuba, Y., Mihira, N., Takano, J., Nilsson, P., Itohara, S., Iwata, N., & Saido, T. C. (2014) · Nature Neuroscience · doi:10.1038/nn.3697 · Cited by 1,447 · cited 1× · see citing works
“Heterozygous 5xFAD, 1 heterozygous APP NLGF , 41 and ATeam 10 mice of both sexes were utilized in this study as stated in further details in corresponding figure legends.”
Aβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M. E., Jäggi, F., Wolburg, H., Gengler, S., et al. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400784 · Cited by 986 · see citing works
Genomic imprinting determines methylation of parental alleles in transgenic mice
Reik, W., Collick, A., Norris, M., Barton, S., & Surani, M. (1987) · Nature · doi:10.1038/328248a0 · Cited by 486 · see citing works
Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Depp, C., Sun, T., Sasmita, A. O., Spieth, L., Berghoff, S. A., Nazarenko, T., Overhoff, K., Steixner-Kumar, A. A., Subramanian, S., Arinrad, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06120-6 · Cited by 476 · see citing works
Self-citationSwain, J. L., Stewart, T., & Leder, P. (1987) · Cell · doi:10.1016/0092-8674(87)90330-8 · Cited by 466 · see citing works
Degree of methylation of transgenes is dependent on gamete of origin
Sapienza, C., Peterson, A., Rossant, J., & Balling, R. (1987) · Nature · doi:10.1038/328251a0 · Cited by 391 · see citing works
Davis, J., Xu, F., Deane, R., Romanov, G., Previti, M. L., Zeigler, K., Zlokovic, B. V., & Van Nostrand, W. E. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312946200 · Cited by 373 · see citing works
Zhao, J., Fu, Y., Yasvoina, M., Shao, P., Hitt, B., O'Connor, T., Logan, S., Maus, E., Citron, M., Berry, R., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4396-06.2007 · Cited by 365 · see citing works
Temporal memory deficits in Alzheimer’s mouse models: Rescue by genetic deletion of BACE1
Ohno, M., Chang, L., Tseng, W., Oakley, H., Citron, M., Klein, W. L., Vassar, R., & Disterhoft, J. F. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04551.x · Cited by 298 · see citing works
Sexual dimorphism in predisposition to Alzheimer's disease
Fisher, D. W., Bennett, D. A., & Dong, H. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.04.004 · Cited by 270 · see citing works
Chaillet, J., Vogt, T., Beier, D., & Leder, P. (1991) · Cell · doi:10.1016/0092-8674(91)90140-t · Cited by 250 · see citing works
Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis.
Sanders, Y., Pardo, A., Selman, M., Nuovo, G., Tollefsbol, T., Siegal, G., & Hagood, J. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0322oc · Cited by 234 · see citing works
Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer’s Disease
Javonillo, D. I., Tran, K. M., Phan, J., Hingco, E., Kramár, E. A., da Cunha, C., Forner, S., Kawauchi, S., Milinkeviciute, G., Gomez-Arboledas, A., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.785276 · Cited by 203 · see citing works
Neuner, S. M., Heuer, S. E., Huentelman, M. J., O’Connell, K. M. S., & Kaczorowski, C. C. (2019) · Neuron · doi:10.1016/j.neuron.2018.11.040 · Cited by 202 · cited 1× · see citing works
“15 Based on our findings, we recommend breeding and maintaining 5xFAD mice by inheriting the transgene through only one germ line—for example, paternally—when a more rapid plaque deposition is desired.”
Goodwin, L., Splinter, E., Davis, T. L., Urban, R., He, H., Braun, R., Chesler, E., Kumar, V., van Min, M., Ndukum, J., et al. (2017) · bioRxiv · doi:10.1101/gr.233866.117 · Cited by 184 · cited 1× · see citing works
“25 30 We are not aware of a study that explicitly investigated allele-specific expression level differences of endogenous Thy1 in the brain.”
Monitoring ATP dynamics in electrically active white matter tracts
Trevisiol, A., Saab, A. S., Winkler, U., Marx, G., Imamura, H., Möbius, W., Kusch, K., Nave, K.-A., & Hirrlinger, J. (2017) · eLife · doi:10.7554/elife.24241 · Cited by 151 · see citing works
Self-citationActive gene sequences are undermethylated.
Naveh‐Many, T., & Cedar, H. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.7.4246 · Cited by 138 · see citing works
Lung, H. L., Bangarusamy, D., Xie, D., Cheung, A., Cheng, Y., Kumaran, M., Miller, L., Liu, E., Guan, X., Sham, J., et al. (2005) · Oncogene · doi:10.1038/sj.onc.1208812 · Cited by 135 · cited 1× · see citing works
“However, it has been shown that methylation changes in the CpG island region of Thy1 contribute to the regulation of Thy1 expression in the context of lung fibrosis, 26 cancer, 31,32 and adipogenesis.”
Sex Differences in Behavior and Molecular Pathology in the 5XFAD Model
Sil, A., Erfani, A., Lamb, N., Copland, R., Riedel, G., & Platt, B. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-210523 · Cited by 109 · see citing works
Bordeleau, M., Lacabanne, C., Fernández de Cossío, L., Vernoux, N., Savage, J. C., González-Ibáñez, F., & Tremblay, M.-È. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01914-1 · Cited by 85 · see citing works
Campsall, K. D., Mazerolle, C. J., Repentingy, Y. D., Kothary, R., & Wallace, V. (2002) · Developmental Dynamics · doi:10.1002/dvdy.10092 · Cited by 71 · see citing works
Bosch, M. E., Dodiya, H. B., Michalkiewicz, J., Lee, C., Shaik, S. M., Weigle, I. Q., Zhang, C., Osborn, J., Nambiar, A., Patel, P., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00700-w · Cited by 70 · see citing works
A DNA signal from the Thy-1 gene defines de novo methylation patterns in embryonic stem cells
Szyf, M., Tanigawa, G., & McCarthy, P. L. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.8.4396-4400.1990 · Cited by 68
In vivo imaging reveals sigmoidal growth kinetic of β-amyloid plaques
Burgold, S., Filser, S., Dorostkar, M. M., Schmidt, B., & Herms, J. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-30 · Cited by 59 · see citing works
Spanopoulou, E., Giguère, V., & Grosveld, F. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.9.3847-3856.1988 · Cited by 37
DNA methylation alters chromatin structure and regulates Thy-1 expression in EL-4 T cells.
Sneller, M., & Gunter, K. (1987) · Journal of Immunology · doi:10.4049/jimmunol.138.10.3505 · Cited by 31 · see citing works
Albert, J. R., Yeung, W. K. A., Toriyama, K., Kobayashi, H., Hirasawa, R., Brind’Amour, J., Bogutz, A., Sasaki, H., & Lorincz, M. C. (2020) · Nature Communications · doi:10.1038/s41467-020-19279-7 · Cited by 28 · see citing works
Valencia‐Olvera, A. C., Balu, D., Bellur, S., McNally, T. P., Saleh, Y., Pham, D., Ghura, S., York, J. M., Johansson, J. O., LaDu, M. J., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01353-z · Cited by 16 · see citing works
Lucero, E., Freund, R. K., Smith, A. N., Johnson, N. R., Dooling, B. R., Sullivan, E. J., Prikhodko, O., Ahmed, M. M., Bennett, D. A., Hohman, T. J., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105288 · Cited by 14 · see citing works
Thy1 (CD90) expression is regulated by DNA methylation during adipogenesis
Flores, E. M., Woeller, C. F., Falsetta, M. L., Susiarjo, M., & Phipps, R. P. (2018) · The FASEB Journal · doi:10.1096/fj.201801481r · Cited by 14 · cited 1× · see citing works
“33 It is also known to a certain extent, however, that the genomic environment impacts transgene expression levels in Thy1.”
Tissue-specific methylation of a CpG island in transgenic mice.
Gundersen, G., Kolstø, A., Larsen, F., & Prydz, H. (1992) · Gene · doi:10.1016/0378-1119(92)90397-8 · Cited by 13
Montanari, M., Carbone, M., Coppola, L., Giuliano, M., Arpino, G., Lauria, R., Nardone, A., Leccia, F., Trivedi, M. V., Garbi, C., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0324 · Cited by 7
SPIN90 Deficiency Ameliorates Amyloid β Accumulation by Regulating APP Trafficking in AD Model Mice
Oh, Y., Lee, W., Kim, S. H., Lee, S., Kim, B. C., Lee, K., Kim, S. H., & Song, W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810563 · Cited by 4 · see citing works
Flagged first, then by citations
8 of the 45 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- [20]20. Sasaki, H., Hamada, T., Ueda, T., Seki, R., Higashinakagawa, T., and Sakaki, Y. (1991). Inherited type of allelic methylation variations in a mouse chromosome region where an integrated transgene shows methylation imprinting. Development 111 , 573-581. https://doi.org/10.1242/dev.111. 2.573. · DOI
- [22]22. Ueda, T., Yamazaki, K., Suzuki, R., Fujimoto, H., Sasaki, H., Sakaki, Y., and Higashinakagawa, T. (1992). Parental methylation patterns of a transgenic locus in adult somatic tissues are imprinted during gametogenesis. Development 116 , 831-839. https://doi.org/10.1242/dev.116.4.831. · DOI
- [23]23. DeLoia, J.A., and Solter, D. (1990). A transgene insertional mutation at an imprinted locus in the mouse genome. Development 108 , 73-79. https:// doi.org/10.1242/dev.108.Supplement.73. · DOI
Cited by
Sorted by citations
Lymphoid gene expression supports neuroprotective microglia function
Ayata, P., Crowley, J. M., Challman, M. F., Sahasrabuddhe, V., Gratuze, M., Werneburg, S., Ribeiro, D., Hays, E. C., Durán-Laforet, V., Faust, T. E., et al. (2025) · Nature · doi:10.1038/s41586-025-09662-z · Cited by 32 · see citing works
Experimental modeling of Alzheimer's disease: Translational lessons from cross‐taxon analyses
Yenkoyan, K. B., Kotova, M. M., Apukhtin, K. V., Galstyan, D. S., Amstislavskaya, T. G., Strekalova, T. V., de Abreu, M. S., Chavushyan, V. A., Lim, L. W., Yang, L., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70273 · Cited by 29 · see citing works
Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy
Chen, Y., Liu, Y. A., Nguyen, K. M., Wu, J., Song, S., Lin, K., Rodrigues, P. F., Du, S., Zhou, C., Xiong, K., et al. (2026) · Science · doi:10.1126/science.ads3972 · Cited by 24 · see citing works
Liver exerkine reverses aging- and Alzheimer’s-related memory loss via vasculature
Bieri, G., Pratt, K. J. B., Fuseya, Y., Aghayev, T., Sucharov, J., Horowitz, A. M., Philp, A. R., Fonseca-Valencia, K., Chu, R., Phan, M., et al. (2026) · Cell · doi:10.1016/j.cell.2026.01.024 · Cited by 30 · see citing works
Chaubey, K., Vázquez‐Rosa, E., Tripathi, S. J., Shin, M., Yu, Y., Dhar, M., Chakraborty, S., Yamakawa, M., Wang, X., Sridharan, P. S., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102535 · Cited by 18 · see citing works
Ramos, J. M. P., Castellani, G., Kviatcovsky, D., Croese, T., Tsitsou-Kampeli, A., Burgaletto, C., Abellanas, M. A., Cahalon, L., Colaiuta, S. P., Salame, T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58494-y · Cited by 15 · see citing works
“…SJL genetic background (Tg6799, MMRRC_034840-JAX; The Jackson Laboratory), overexpressing familial AD mutant forms of human APP and PS1 transgenes under the transcriptional control of neural-speci fi c elements of the mouse Thy1 promoter 100 , were used with a paternal transgenic inheritance 101 .”
Immunity in Alzheimer’s disease: From mechanisms to therapies
Chen, X., Holtzman, D. M., & Colonna, M. (2026) · Immunity · doi:10.1016/j.immuni.2026.02.004 · Cited by 17 · see citing works
Guo, Z., Ni, H., Yu, L., Cui, Z., Wang, Y., Zhu, Z., Wei, X., Xia, C., Xu, M., Du, L., et al. (2025) · Advanced Science · doi:10.1002/advs.202510885 · Cited by 8 · see citing works
A decade progress in the phenotyping of App knock-in mouse model of Alzheimer’s disease
Manabe, T., & Saito, T. (2025) · Neuroscience Research · doi:10.1016/j.neures.2025.104959 · Cited by 14 · see citing works
Calcines-Rodríguez, L., Noyes-Martel, N., Becker, J. D., Nguyen, S. K., Osabutey, M., Trojanczyk, L., Majewska, A. K., & O’Banion, M. K. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03659-1 · Cited by 7 · see citing works
“Hemizygous 5xFAD female mice were bred with C57BL6/J male wild-type (WT) mice (JAX: 000664) to generate the experimental mice used in this study and to ensure that the parental origin of the trans-gene was similar across all progeny [56].”
Microglial CLEC7A restrains amyloid beta plaque pathology in a mouse model of Alzheimer's disease
Mangalmurti, A., Zengeler, K. E., Hollis, A., Golden, E., Riddlemoser, G., & Lukens, J. R. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70943 · Cited by 9 · see citing works
Ferreira, A. F. F., Santos-Silva, A. C., Muratori, B. G., & Britto, L. R. G. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1733682 · Cited by 5 · see citing works
“Transgenic inheritance modulates transgene expression, and A β levels may be higher when the transgene is inherited paternally rather than maternally (Sasmita et al., 2025).”
Titze‐de‐Almeida, R., Gomes, G. D. M. O., dos Santos, T. C., & Titze-de-Almeida, S. S. (2025) · Pharmaceuticals · doi:10.3390/ph19010026 · Cited by 5 · see citing works
“Nevertheless, as with other neurodegenerative disease models, it has limitations that may hinder its capacity to fully represent the complex spectrum of the disease, as discussed in other reviews [134–137].”
Shajahan, S. R., Hamid, N., Okunsai, B., Shari, N., & Ramli, M. D. C. (2026) · Biomedicines · doi:10.3390/biomedicines14040860 · Cited by 4 · see citing works
“…central to diagnostic frameworks and biomarker development, it is noteworthy that in some cases, post-mortem analyses reveal A β accumulation without preceding clinical signs of cognitive impairment, indicating that amyloid deposition alone is not always predictive of symptomatic disease [24,25].”
Li, Y., Wang, H., Zhang, D., Wang, S., Li, Z., Li, J.-J., Tai, S., Tong, D.-D., Wang, B., Lu, D., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-68937-9 · Cited by 4 · see citing works
A Question of Origins: Non-neuronal Sources of Amyloid-β
Sasmita, A. O., & Depp, C. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-025-01572-4 · Cited by 3 · see citing works
“In view of the sigmoidal growth kinetics of Aβ plaques observed within in vivo studies [83, 84], Aβ plaques seem to only manifest once a certain threshold parenchymal Aβ concentration is surpassed and significant volumetric growth occurs at high Aβ concentration.”
Self-citationNeuharth, J., Hernandez, K., Bernholtz, J., Edwards, H., & Stewart, A. (2025) · Biology of Sex Differences · doi:10.1186/s13293-025-00788-3 · Cited by 4 · see citing works
INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia
Terzioglu, G., Karp, E. S., Heuer, S. E., Chadarevian, J. P., Ahsan, F. M., Haage, V. C., Davtyan, H., Fogo, G. M., Curle, A. J., Ashour, N., et al. (2025) · doi:10.1101/2025.10.27.684632 · Cited by 3 · see citing works
Esteban, S. R. D. M., Grande, M. T., Martínez-Relimpio, A. M., Herráez‐Aguilar, D., Mostany, R., Hillard, C. J., Hind, W. H., & Romero, J. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118902 · Cited by 4 · see citing works
Unmasking early microglial remodeling in an Alzheimer’s disease mouse model
Saminathan, P., McArdle, S., Corey, M., Nadig, N., Fang, C., Gibbons, A., Rayadurgam, M., & Sharma, S. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1720382 · Cited by 3 · see citing works
Shiyab, A., & Reed, E. G. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27135990 · Cited by 2
García-Peña, P., Ramos, M., López, J. M., Martínez‐Murillo, R., de Arcas, G., & González‐Nieto, D. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107484 · Cited by 1 · see citing works
Embalabala, R., Masters, H., Ziehm, E. M., Pouncey, J., Kim, H., & Lippmann, E. S. (2026) · Fluids and Barriers of the CNS · doi:10.1186/s12987-026-00766-w · Cited by 1 · see citing works
“Although the 5XFAD model was originally developed on a mixed, C57BL/6J x SJL/J F1 hybrid background, there has been a preferential shift in the literature towards a pure C57BL/6J background [30].”
Maternal Inheritance Suppresses CAA and Amyloid Plaques in 5xFAD (Tg7031)/APOE4 Mice
Saadi, F., Katritch, I. V., Parhizkar, S., Lugo, B., Cho, Y., Ulrich, J. D., & Holtzman, D. (2025) · Neuron · doi:10.1016/j.neuron.2025.08.008 · Cited by 2 · see citing works
Boyanova, S., Katsouri, L., Krupic, J., Hair, K., Wang, S., & Wiseman, F. K. (2026) · STAR Protocols · doi:10.1016/j.xpro.2026.104633 · Cited by 1 · see citing works
“58 61 Moreover, APP cleavage products, in addition to amyloid-β , are elevated in transgenic APP models, including the widely used 5xFAD and APP Swe /PSEN1 dE9 lines.”
Astrocytic Activation Completely Corrects Memory Performance in an Alzheimer’s Disease ModelPreprint
Kreisel, T., Weinstein, Y., Groysman, M., Doron, A., Refaeli, R., London, M., & Goshen, I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.29.679133 · Cited by 2 · see citing works
“They were bred with a heterozygous 5XFAD male and a WT female, as recommended (Sasmita et al., 2025), and the littermates were genotyped.”
Chen, K., Chen, Y., Ren, Y., Wang, Z., Huang, Y., Pan, M., Li, Z., Casey, M. C., Qiao, W., Shi, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-78407-x
Behavioral characterization of 5xFAD mice using standardized decision-making and open field assays
Imomdodova, N., Korde, S., Lee, Y.-J., Cinquemani, S., & Hwang, E. (2026) · Scientific Reports · doi:10.1038/s41598-026-75840-2
“Parental origin has been shown to influence amyloid plaque burden in 5xFAD mice 58 , and we observed substantial inter-individual variability in plaque burden among age-matched animals.”
Park, T., Chang, L., Chung, S. W., Lee, S., Bae, S., Condello, C., Kim, Y. H., Lee, J., Kim, H.-J., Kwon, H.-K., et al. (2026) · Science Advances · doi:10.1126/sciadv.adx0731
Revisiting the role of amyloid-β: A molecular and immunological perspective
Slama, P. S. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261484863
“228 In addition, glial cells from rodents are quite different from those present in human brains.”
Kalluri, V. S., Che, S. P. Y., Conner, M. R., Diaz, B. M., Yarlagadda, A., Church, K. A., Chronopoulos, A., Vázquez-Arreguín, K., Sugimoto, H., & Kalluri, R. (2026) · bioRxiv · doi:10.64898/2026.08.10.744066
Tau reduction counteracts transcriptomic and behavioral abnormalities in an Alzheimer amyloid modelPreprint
Knowles, S. J., Sant, C., Nambiar, P., Gonçalves, R. A., Ho, K., Yu, G.-Q., Thomas, R., Mori, M., Domke, L., Huang, V., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.03.741071
“41 ) reduced their numbers in the cohort of mice we had generated.”
InfluentialPlaque-associated microglial polarization in visual brain regions of the 5xFAD mouse model
McCool, S., Jain, A., Smith, J. C., & Hook, M. J. V. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1824891
“Additionally, it has been shown that transgene inheritance in this model plays a role in A β plaque burden which suggests it could play a role in plaque patterning, both temporally and spatially, as well (Gregg et al., 2010; Sasmita et al., 2025).”
Keller-Norrell, P. R., Casali, B., Yost, L. N., & Reed, E. G. (2026) · Biology of Sex Differences · doi:10.1186/s13293-026-00948-z
“Images focused on cortical layer V, as this layer is particularly vulnerable to neuronal atrophy and cell death in the 5xFAD [23].”
Hunting for an Antigen: Humoral Immunity in Alzheimer’s Disease
Delgado, A. M., Greer, B. D., Maul, R. W., & Gearhart, P. J. (2026) · Cells · doi:10.3390/cells15131227
Zhang, X., Zhuang, D., Lai, C., Zheng, C., Soh, Z. D., Wagner, S. K., Cai, V. Y., Yang, Z., Wang, S., Geng, X., et al. (2026) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2026.101504
Javonillo, D. I., Furman, S., Le, L., Fernandez, K., Mulford, J., Singla, V., Jha, R., Tsourmas, K., Kwang, N. E., Green, K. N., et al. (2026) · Alzheimer's & Dementia · doi:10.1002/alz.71637
Yan, Y., Song, D., Li, G.-F., Li, J., Tang, Y., Li, D., Mao, J., Li, H., Liu, X.-Y., Yu, D., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03550-2
“All efforts were made to minimize the number of animals used.”
Better understanding of laboratory animal genetics will improve reproducibility
Pavlovic, G., Wells, S., Hérault, Y., & Teboul, L. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003464
“Genomic verification of both the genetic background and the modified allele is essential and, in the case of engineered alleles, so too is the validation of the presumed functional outcome [2,4].”
InfluentialGallardo, D., & Steward, O. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.04.647232
Parent-of-origin of alleles: an essential variable in in vivo experiments
Teboul, L., & Stewart, M. E. (2025) · Lab Animal · doi:10.1038/s41684-025-01546-z
Parental origin of transgene determines recombination efficiency in GFAP-creERT2 mice
Mah, K., Roszczyk, A., & Frakes, A. E. (2025) · bioRxiv · doi:10.1101/2025.02.27.640655
“For example, in the widely used 5XFAD mouse model of Alzheimer’s disease, 5XFAD mice exhibit a more severe phenotype if the transgene is paternally inherited (Sasmita et al., 2025).”
Montanari, S. (2025) · The Transmitter · doi:10.53053/qlmb2680
Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis
Walsh, A. E., Davis, B. A., Samuels, J. D., Mills, W. A., Thanos, J. M., Johnson, A. M., Moore, K. A., Puchalski, M. A., Steacy, E. J., Wendell, B. W., et al. (2026) · Journal of Experimental Medicine · doi:10.1084/jem.20260104
- Authors
- Sasmita, A. O., Ong, E. C., Nazarenko, T., Mao, S., Komarek, L., Thalmann, M., Hantakova, V., Spieth, L., Berghoff, S. A., Barr, H. J., Hingerl, M., Börensen, F., Hirrlinger, J., Simons, M., Stevens, B., Depp, C., & Nave, K.-A.
- Affiliations
- Max Planck Society (DE)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- German Center for Neurodegenerative Diseases (DE)
- University of Göttingen (DE)
- Boston Children's Hospital (US)
- Broad Institute (US)
- Corresponding author
- Sasmita, Andrew Octavian
- Depp, Constanze
- Nave, Klaus-Armin
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2025-03
- Volume
- 113
- Issue
- 6
- Pages
- 838-846.e4
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W4406608755
- Cited by
- 42
- References
- 45
- Citations by year
- 2026: 23 · 2025: 19
- FWCI
- 27.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- DZNE Pub (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion)
- Funders
- European Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, 5xFAD mice, amyloid plaques, paternal inheritance, maternal inheritance, genomic imprinting, transgene expression, breeding strategies, reproducibility
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Transgenes, Mice, Plaque, Amyloid
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
