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Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease
Abstract
Biochemical and genetic evidence implicate soluble oligomeric amyloid-β (Aβo) in triggering Alzheimer's disease (AD) pathophysiology. Moreover, constitutive deletion of the Aβo-binding cellular prion protein (PrP C ) prevents development of memory deficits in APP swe /PS1ΔE9 mice, a model of familial AD. Here, we define the role of PrP C to rescue or halt established AD endophenotypes in a therapeutic disease-modifying time window after symptom onset. Deletion of Prnp at either 12 or 16 months of age fully reverses hippocampal synapse loss and completely rescues preexisting behavioral deficits by 17 months. In contrast, but consistent with a neuronal function for Aβo/PrP C signaling, plaque density, microgliosis, and astrocytosis are not altered. Degeneration of catecholaminergic neurons remains unchanged by PrP C reduction after disease onset. These results define the potential of targeting PrP C as a disease-modifying therapy for certain AD-related phenotypes after disease onset. SIGNIFICANCE STATEMENT The study presented here further elucidates our understanding of the soluble oligomeric amyloid-β–Aβo-binding cellular prion protein (PrP C ) signaling pathway in a familial form of Alzheimer's disease (AD) by implicating PrP C as a potential therapeutic target for AD. In particular, genetic deletion of Prnp rescued several familial AD (FAD)-associated phenotypes after disease onset in a mouse model of FAD. This study underscores the therapeutic potential of PrP C deletion given that patients already present symptoms at the time of diagnosis.
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Conditional deletion of the oligomer receptor PrPc in Alzheimer transgenic mice rescues cognitive and synaptic deficits.
“Conditional deletion of the oligomer receptor PrPc in Alzheimer transgenic mice rescues cognitive and synaptic deficits [128].”
From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [128]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
RetractedNeuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123
Experience-dependent structural synaptic plasticity in the mammalian brain
Holtmaat, A., & Svoboda, K. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2699 · Cited by 1,934
Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures
Cummings, J. L., Morstorf, T., & Zhong, K. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt269 · Cited by 1,744
Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009) · Nature · doi:10.1038/nature07761 · Cited by 1,560
Self-citationCurrent and future treatments for Alzheimer's disease
Yiannopoulou, K. G., & Papageorgiou, S. G. (2013) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285612461679 · Cited by 677
Um, J. W., Kaufman, A. C., Kostylev, M., Heiss, J. K., Stagi, M., Takahashi, H., Kerrisk, M. E., Vortmeyer, A., Wisniewski, T., Koleske, A. J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.036 · Cited by 572
Self-citationSynthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein
Balducci, C., Beeg, M., Stravalaci, M., Bastone, A., Sclip, A., Biasini, E., Tapella, L., Colombo, L., Manzoni, C., Borsello, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911829107 · Cited by 466
Synapses and Alzheimer's Disease
Sheng, M., Sabatini, B. L., & Sudhof, T. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005777 · Cited by 436
Fyn inhibition rescues established memory and synapse loss in Alzheimer mice
Kaufman, A. C., Salazar, S. V., Haas, L. T., Yang, J., Kostylev, M. A., Jeng, A. T., Robinson, S. A., Gunther, E. C., van Dyck, C. H., Nygaard, H. B., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24394 · Cited by 314
Self-citationThe prion protein as a receptor for amyloid-β
Kessels, H. W., Nguyen, L. N., Nabavi, S., & Malinow, R. (2010) · Nature · doi:10.1038/nature09217 · Cited by 253
Prion protein and Aβ‐related synaptic toxicity impairment
Calella, A. M., Farinelli, M., Nuvolone, M., Mirante, O., Moos, R., Falsig, J., Mansuy, I. M., & Aguzzi, A. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000082 · Cited by 242
Jankowsky, J. L., Slunt, H. H., Gonzales, V., Savonenko, A. V., Wen, J. C., Jenkins, N. A., Copeland, N. G., Younkin, L. H., Lester, H. A., Younkin, S. G., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020355 · Cited by 237
Kostylev, M. A., Kaufman, A. C., Nygaard, H. B., Patel, P., Haas, L. T., Gunther, E. C., Vortmeyer, A., & Strittmatter, S. M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.643577 · Cited by 133
Self-citationKlyubin, I., Nicoll, A. J., Khalili-Shirazi, A., Farmer, M., Canning, S., Mably, A., Linehan, J., Brown, A., Wakeling, M., Brandner, S., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3526-13.2014 · Cited by 74
Flagged first, then by citations
Research works printed but not linked: 43
- 10.1111/jnc.13166 · DOI
- 10.1016/j.jalz.2012.02.001 · DOI
- 10.1523/JNEUROSCI.6500-10.2011 · DOI · Paper page
- 10.1523/JNEUROSCI.4195-09.2009 · DOI
- 10.1074/jbc.M110.145516 · DOI
- 10.1186/1471-2202-11-130 · DOI · Paper page
- 10.1093/brain/awt375 · DOI
- 10.1016/j.brainres.2009.07.066 · DOI · Paper page
- 10.1074/jbc.M112.423954 · DOI
- 10.1523/JNEUROSCI.0572-14.2014 · DOI
- 10.1038/ncomms1341 · DOI
- 10.1523/JNEUROSCI.0395-10.2010 · DOI · Paper page
- 10.1093/brain/awv356 · DOI
- 10.1126/science.1072994 · DOI · Paper page
- 10.1006/dbio.2002.0597 · DOI
- Heiss, 2017, Early activation of experience-independent dendritic spine turnover in a mouse model of Alzheimer's disease, Cereb Cortex, 7, 3660
- 10.1016/S0960-9822(02)01077-1 · DOI
- 10.1038/ncomms4374 · DOI
- 10.1073/pnas.95.11.6448 · DOI · Paper page
- 10.1523/JNEUROSCI.1858-12.2012 · DOI
- 10.1523/JNEUROSCI.4218-08.2008 · DOI · Paper page
- 10.1523/JNEUROSCI.1694-14.2014 · DOI · Paper page
- 10.1146/annurev.neuro.26.043002.094919 · DOI
- 10.1523/JNEUROSCI.4251-12.2013 · DOI
- Mölsä, 1986, Survival and cause of death in Alzheimer's disease and multi-infarct dementia, Acta Neurol Scand, 74, 103, 10.1111/j.1600-0404.1986.tb04634.x · DOI
- 10.1523/JNEUROSCI.4825-12.2013 · DOI · Paper page
- 10.1186/s13195-015-0110-9 · DOI
- 10.1016/j.neuropharm.2015.09.030 · DOI
- 10.1523/JNEUROSCI.4504-06.2006 · DOI
- 10.1186/1750-1326-7-28 · DOI
- 10.1093/emboj/20.4.694 · DOI
- 10.1074/jbc.M112.400358 · DOI
- 10.1016/j.neurobiolaging.2005.09.012 · DOI · Paper page
- 10.1177/002215549904700601 · DOI
- 10.1126/science.1074069 · DOI · Paper page
- 10.1101/cshperspect.a004457 · DOI
- 10.1038/nm1782 · DOI · Paper page
- 10.1101/cshperspect.a024075 · DOI · Paper page
- 10.1002/gene.20046 · DOI
- 10.1038/nn.3178 · DOI
- 10.1038/416535a · DOI · Paper page
- 10.1523/JNEUROSCI.1034-15.2015 · DOI
- 10.3233/JAD-2012-120151 · DOI
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The probabilistic model of Alzheimer disease: the amyloid hypothesis revised
Frisoni, G. B., Altomare, D., Thal, D. R., Ribaldi, F., van der Kant, R., Ossenkoppele, R., Blennow, K., Cummings, J., van Duijn, C., Nilsson, P. M., et al. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00533-w · Cited by 513
Hippocampal Deficits in Amyloid-β-Related Rodent Models of Alzheimer’s Disease
Vyas, Y., Montgomery, J. M., & Cheyne, J. E. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00266 · Cited by 66
Lizama, B. N., Kahle, J., Catalano, S. M., Caggiano, A. O., Grundman, M., & Hamby, M. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076251 · Cited by 54
Metadata
- Authors
- Salazar, S. V., Gallardo, C., Kaufman, A. C., Herber, C. S., Haas, L. T., Robinson, S., Manson, J. C., Lee, M. K., & Strittmatter, S. M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2017-08-21
- Volume
- 37
- Issue
- 38
- Pages
- 9207-9221
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 55
- References
- 15
- Language
- en
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