BIN1 Genetic Risk Factor for Alzheimer is Sufficient to Induce Early Structural Tract Alterations in Entorhinal-Hippocampal Area and Memory-Related Hippocampal Multi-Scale Impairments
Open accessAbstract
Genetic factors are known to contribute to Late Onset Alzheimer’s disease (LOAD) but their contribution to pathophysiology, specially to prodomic phases accessible to therapeutic approaches are far to be understood. To translate genetic risk of Alzheimer’s disease (AD) into mechanistic insight, we generated transgenic mouse lines that express a ∼195 kbp human BAC that includes only BIN1 , a gene associated to LOAD. This model gives a modest BIN1 overexpression, dependent of the number of BAC copies. At 6 months of age, we detected impaired entorhinal cortex (EC)-hippocampal pathways with specific impairments in EC-dentate gyrus synaptic long-term potentiation, dendritic spines of granular cells and recognition episodic memory. Structural changes were quantified using MRI. Their whole-brain functional impact were analyzed using resting state fMRI with a hypoconnectivity centered on entorhinal cortex. These early phenotype defects independent of any changes in A-beta can be instrumental in the search for new AD drug targets.
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Increased expression of BIN1 in mice is associated with alterations in dendritic spine density and LTP dysregulation.
“Finally, increased expression of BIN1 in mice has also been associated with alterations in dendritic spine density and in LTP dysregulation [22].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [22]
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Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · see citing works
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · see citing works
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984) · Science · doi:10.1126/science.6474172 · Cited by 2,268 · see citing works
What does the retrosplenial cortex do?
Vann, S. D., Aggleton, J. P., & Maguire, E. A. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2733 · Cited by 1,409 · see citing works
Memory engrams: Recalling the past and imagining the future
Josselyn, S. A., & Tonegawa, S. (2020) · Science · doi:10.1126/science.aaw4325 · Cited by 1,087 · see citing works
Grubman, A., Chew, G., Ouyang, J. F., Sun, G., Choo, X. Y., McLean, C., Simmons, R. K., Buckberry, S., Vargas-Landin, D. B., Poppe, D., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0539-4 · Cited by 956 · see citing works
Staging of Alzheimer-Related Cortical Destruction
Braak, H., Braak, E., & Bohl, J. (2008) · European Neurology · doi:10.1159/000116984 · Cited by 836 · see citing works
Quantitative proteomics reveals subset-specific viral recognition in dendritic cells
Luber, C. A., Cox, J., Lauterbach, H., Fancke, B., Selbach, M., Tschopp, J., Akira, S., Wiegand, M., Hochrein, H., O'Keeffe, M., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.01.013 · Cited by 576 · see citing works
Khan, U. A., Liu, L., Provenzano, F. A., Berman, D. E., Profaci, C. P., Sloan, R., Mayeux, R., Duff, K. E., & Small, S. A. (2014) · Nature Neuroscience · doi:10.1038/nn.3606 · Cited by 561 · see citing works
Structural plasticity upon learning: regulation and functions
Caroni, P., Donato, F., & Muller, D. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3258 · Cited by 491 · see citing works
Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes
Chung, W.-S., Verghese, P. B., Chakraborty, C., Joung, J., Hyman, B. T., Ulrich, J. D., Holtzman, D. M., & Barres, B. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1609896113 · Cited by 242 · 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 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- [1]1. Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
- [2]2. Dembélé, D. & Kastner, P. Fold change rank ordering statistics: a new method for detecting differentially expressed genes. BMC Bioinformatics 15, 14 (2014).
- [7]7. Ferreira, T. A. et al. Neuronal morphometry directly from bitmap images. Nat. Methods 11, 982984 (2014).
Cited by
Sorted by citations
Dourlen, P., Kilinc, D., Malmanche, N., Chapuis, J., & Lambert, J.-C. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02004-0 · Cited by 168 · see citing works
Sartori, M., Mendes, T., Desai, S., Lasorsa, A., Herledan, A., Malmanche, N., Mäkinen, P., Marttinen, M., Malki, I., Chapuis, J., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02017-9 · Cited by 72 · see citing works
Self-citation
- Authors
- Daudin, R., Marechal, D., Golgolab, R., Wang, Q., Abe, Y., Tsurugizawa, T., Bourg, N., Sartori, M., Loe-Mie, Y., Lipecka, J., Guerrera, C., McKenzie, A., Potier, B., Dutar, P., Viard, J., Lepagnol-Bestel, A. M., Winkeler, A., Uszynski, I., Hindié, V, Birling, M., Lindner, L., Chevalier, C., Pavlovic, G., Reiss, M., Kranz, H., Dupuis, G., Lévêque-Fort, S., Diaz, J., Davenas, E., Dembele, D., Atas-Ozcan, H., Laporte, J., Thibault-Carpentier, C., Malissen, B., Rain, J. C., Poupon, C., Le Bihan, D., Zhang, B., Herault, Y., Ciobanu, L., & Simonneau, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Icahn School of Medicine at Mount Sinai (US)
- Inserm (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Hybrigenics (France) (FR)
- Gene Bridges (Germany) (DE)
- École Normale Supérieure Paris-Saclay (FR)
- Corresponding author
- Simonneau, M
- ORCID
- Venue
- SSRN Electronic Journal
- Publisher
- openRxiv
- Published
- 2018-10-08
- ISSN
- 1556-5068 (ISSN-L)
- OpenAlex
- W2895305250
- Cited by
- 14
- References
- 13
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- SSRN Electronic Journal (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-18-ENM3-0002, ANR-17-JPCD-0002)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- BIN1, late-onset Alzheimer's disease, genetic risk factors, transgenic mouse model, entorhinal cortex, hippocampus, dentate gyrus, long-term potentiation, dendritic spines, episodic memory, structural MRI, resting-state fMRI, prodromal Alzheimer's disease, therapeutic target
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