Neuronal Pentraxin 1 Contributes to the Neuronal Damage Evoked by Amyloid-β and Is Overexpressed in Dystrophic Neurites in Alzheimer's Brain
Open accessAbstract
Accumulation of amyloid-β (Aβ) is thought to play a central role in the progressive loss of synapses, the neurite damage, and the neuronal death that are characteristic in brains affected by Alzheimer's disease. However, the mechanisms through which Aβ produces such neurotoxicity remain unclear. Because Aβ depresses synaptic activity, we investigated whether the neurotoxicity of Aβ depends on the expression of NP1, a protein involved in excitatory synapse remodeling that has recently been shown to mediate neuronal death induced by reduction in neuronal activity in mature neurons. We found that treatment of cortical neurons in culture with Aβ produces a marked increase in NP1 protein that precedes apoptotic neurotoxicity. Silencing NP1 gene expression by RNA interference (short hairpin RNA for RNA interference) prevents the loss of synapses, the reduction in neurite outgrowth, and the apoptosis evoked by Aβ. Transgene overexpression of NP1 reproduced these neurotoxic effects of Aβ. Moreover, we found that NP1 was increased in dystrophic neurites of brains from patients with sporadic late-onset Alzheimer's disease. Dual immunohistochemistry for NP1 and tau showed that NP1 colocalizes with tau deposits in dystrophic neurites. Furthermore, NP1 colocalized with SNAP-25 (synaptosomal-associated protein of 25 kDa) in the majority of dystrophic neurites surrounding amyloid deposits. NP1 was also increased in cell processes surrounding amyloid plaques in the cerebral cortex and hippocampus of APP/PS1 (mutant amyloid precursor protein/presenilin 1) transgenic mice. These findings show that NP1 is a key factor for the synapse loss, the neurite damage, and the apoptotic neuronal death evoked by Aβ and indicate that Aβ contributes to the pathology of Alzheimer's disease by regulating NP1 expression.
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NPTX1 is present in neuronal projections, mainly in the pre-synaptic terminal, including mossy fibres, stratum lucidum of CA3, and stratum radiatum of CA1.
“With regards to its cellular localisation in the cerebral cortex, NPTX1 is present in neuronal projections, mainly in the pre-synaptic terminal; in particular, in the mossy fibres projecting from granule cells to the dentate gyrus, in the stratum lucidum of CA3 and stratum radiatum of CA1.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Abad et al. 2006
NPTXs might underly some of the neurotoxic effects of Aβ aggregation.
“NPTXs might also underly some of the neurotoxic effects of Aβ aggregation (Abad et al. 2006), which is known to affect excitatory synaptic transmission and neuronal activity, mechanisms that precede neurite degeneration and neuronal death (Kamenetz et al. 2003; Walsh and Selkoe 2004) and subsequent cognitive failure (Driscoll and Troncoso 2011; Jack and Holtzman 2013).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Abad et al. 2006
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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 Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420 · see citing works
Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R. (1982) · Science · doi:10.1126/science.7058341 · Cited by 3,627 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
RNA interference is mediated by 21- and 22-nucleotide RNAsPreprint
Elbashir, S. M., Lendeckel, W., & Tuschl, T. (2001) · Genes & Development · doi:10.1101/gad.862301 · Cited by 3,308 · see citing works
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376 · see citing works
Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides
Yankner, B. A., Duffy, L. K., & Kirschner, D. A. (1990) · Science · doi:10.1126/science.2218531 · Cited by 1,975 · see citing works
Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery
Zufferey, R., Dull, T., Mandel, R. J., Bukovsky, A., Quiroz, D., Naldini, L., & Trono, D. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9873-9880.1998 · Cited by 1,815 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201750200 · Cited by 1,452 · see citing works
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207 · see citing works
Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.
Loo, D. T., Copani, A., Pike, C. J., Whittemore, E. R., Walencewicz, A. J., & Cotman, C. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.7951 · Cited by 1,022 · see citing works
Hartley, D. M., Walsh, D. M., Ye, C., Diehl, T. S., Vasquez, S., Vassilev, P., Teplow, D. B., & Selkoe, D. J. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-20-08876.1999 · Cited by 965 · see citing works
D'Mello, S. R., Galli, C., Ciotti, T., & Calissano, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10989 · Cited by 892 · see citing works
Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease
Masliah, E., Mallory, M., Alford, M., DeTeresa, R., Hansen, L. A., McKeel, D. W., & Morris, J. C. (2001) · Neurology · doi:10.1212/wnl.56.1.127 · Cited by 720 · see citing works
Wiznerowicz, M., & Trono, D. (2003) · Journal of Virology · doi:10.1128/jvi.77.16.8957-8951.2003 · Cited by 703 · see citing works
Pike, C. J., Walencewicz‐Wasserman, A. J., Kosmoski, J., Cribbs, D. H., Glabe, C. G., & Cotman, C. W. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64010253.x · Cited by 699 · see citing works
Davies, C. A., Mann, D. M. A., Sumpter, P. Q., & Yates, P. O. (1987) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(87)90057-8 · Cited by 628 · see citing works
Bhat, R. V., Xue, Y., von Berg, S., Hellberg, S., Ormö, M., Nilsson, Y., Radesäter, A., Jerning, E., Markgren, P.-O., Borgegård, T., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306268200 · Cited by 557 · see citing works
Aβ toxicity in Alzheimer’s disease: globular oligomers (ADDLs) as new vaccine and drug targets
Klein, W. L. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(02)00050-5 · Cited by 541 · see citing works
Roher, A. E., Chaney, M. O., Kuo, Y., Webster, S. D., Stine, W. B., Haverkamp, L. J., Woods, A. S., Cotter, R. J., Tuohy, J. M., Krafft, G. A., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.34.20631 · Cited by 494 · see citing works
MORISHIMA, Y., Gotoh, Y., Zieg, J., Barrett, T., Takano, H., Flavell, R. A., Davis, R. J., Shirasaki, Y., & Greenberg, M. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07551.2001 · Cited by 484 · see citing works
Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product narp.
O’Brien, R. J., Xu, D., Petralia, R. S., Steward, O., Huganir, R. L., & Worley, P. (1999) · Neuron · doi:10.1016/s0896-6273(00)80782-5 · Cited by 471 · see citing works
Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain
Takahashi, R. H., Almeida, C. G., Kearney, P. F., Yu, F., Lin, M. T., Milner, T. A., & Gouras, G. K. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5167-03.2004 · Cited by 445 · see citing works
Glycogen synthase kinase 3: a drug target for CNS therapies
Bhat, R. V., Haeberlein, S. L. B., & Ávila, J. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02422.x · Cited by 408 · see citing works
Tau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity.
Takashima, A., Noguchi, K., Sato, K., Hoshino, T., & Imahori, K. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.16.7789 · Cited by 381 · see citing works
Osmand, A., Friedenson, B., Gewurz, H., Painter, R. H., Hofmann, T., & Shelton, E. (1977) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.74.2.739 · Cited by 350 · see citing works
Tsui, C., Copeland, N., Gilbert, D., Jenkins, N., Barnes, C., & Worley, P. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-08-02463.1996 · Cited by 315 · see citing works
Takashima, A., Honda, T., Yasutake, K., Michel, G., Murayama, O., Murayama, M., Ishiguro, K., & Yamaguchi, H. (1998) · Neuroscience Research · doi:10.1016/s0168-0102(98)00061-3 · Cited by 287 · see citing works
Lithium protects cultured neurons against β‐amyloid‐induced neurodegeneration
Alvarez, G., Muñoz-Montaño, J. R., Satrústegui, J., Ávila, J., Bogónez, E., & Díaz‐Nido, J. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00685-7 · Cited by 270 · see citing works
Xu, D., Hopf, C., Reddy, R., Cho, R. W., Guo, L., Lanahan, A., Petralia, R. S., Wenthold, R. J., O'Brien, R. J., & Worley, P. (2003) · Neuron · doi:10.1016/s0896-6273(03)00463-x · Cited by 265 · see citing works
Engel, T., Hernández, F., Ávila, J., & Lucas, J. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0604-06.2006 · Cited by 261 · see citing works
Estus, S., Tucker, H. M., van Rooyen, C., Wright, S., Brigham, E. F., Wogulis, M. D., & Rydel, R. E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-20-07736.1997 · Cited by 255 · see citing works
Wei, W., Wang, X., & Kusiak, J. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111704200 · Cited by 190 · see citing works
Neuronal Pentraxins Mediate Synaptic Refinement in the Developing Visual System
Bjartmar, L., Huberman, A. D., Ullian, E. M., Renteria, R. C., Liu, X., Xu, W., Prezioso, J., Susman, M. W., Stellwagen, D., Stokes, C. C., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4212-05.2006 · Cited by 179 · see citing works
Dodds, D. C., Omeis, I. A., Cushman, S. J., Helms, J. A., & Perin, M. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21488 · Cited by 170 · see citing works
A simple procedure for quantification of neurite outgrowth based on stereological principles
Rønn, L. C. B., Ralets, I., Hartz, B. P., Bech, M., Berezin, A., Berezin, V., Møller, A., & Bock, E. (2000) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(00)00228-4 · Cited by 167 · see citing works
Ivins, K. J., Bui, E. T. N., & Cotman, C. W. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0228 · Cited by 164 · see citing works
Neuronal pentraxin, a secreted protein with homology to acute phase proteins of the immune system
Schlimgen, A. K., Helms, J. A., Vogel, H. S., & Perin, M. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90308-9 · Cited by 163 · see citing works
Biochemical Interactions of the Neuronal Pentraxins
Kirkpatrick, L., Matzuk, M. M., Dodds, D. C., & Perin, M. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002254200 · Cited by 149 · see citing works
Wei, H., Leeds, P. R., Qian, Y., et al. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00127-8 · Cited by 127 · see citing works
Tau protein I is essential for amyloid β-protein iduced neurotoxicity
Takashima, A. (1993) · Medical Entomology and Zoology · Cited by 125 · see citing works
Harnessing HIV for therapy, basic research and biotechnology.
Wiznerowicz, M., & Trono, D. (2005) · Trends in Biotechnology · doi:10.1016/j.tibtech.2004.11.001 · Cited by 113 · see citing works
Human Neuronal Pentraxin II (NPTX2): Conservation, Genomic Structure, and Chromosomal Localization
Hsu, Y., & Perin, M. S. (1995) · Genomics · doi:10.1006/geno.1995.1134 · Cited by 103 · see citing works
Temporal Sequence of Alzheimer’s Disease-Related Pathology
Braak, H., & Braak, E. (1999) · Cerebral cortex · doi:10.1007/978-1-4615-4885-0_14 · Cited by 94 · see citing works
DeGregorio-Rocasolano, N., Gasull, T., & Trullas, R. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007967200 · Cited by 56 · see citing works
Self-citationEnguita, M., DeGregorio‐Rocasolano, N., Abad, A., & Trullás, R. (2005) · Molecular Pharmacology · doi:10.1124/mol.104.007062 · Cited by 50 · see citing works
Self-citationFerrer, I., Martı́, E., Tortosa, A., & Blasi, J. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199803000-00002 · Cited by 49 · see citing works
Self-citationChen, B., & Bixby, J. L. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4365-04.2005 · Cited by 25 · see citing works
Rudolph, J. G., Lemasters, J. J., & Crews, F. T. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(96)13313-9 · Cited by 24 · see citing works
Chen, B., & Bixby, J. L. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20391 · Cited by 22 · see citing works
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Swiech, L., Perycz, M., Malik, A., & Jaworski, J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.015 · Cited by 338 · see citing works
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Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
Yin, G. N., Lee, H. W., Cho, J.-Y., & Suk, K. (2009) · Brain Research · doi:10.1016/j.brainres.2009.01.058 · Cited by 143 · see citing works
Duits, F. H., Brinkmalm, G., Teunissen, C. E., Brinkmalm, A., Scheltens, P., Van der Flier, W. M., Zetterberg, H., & Blennow, K. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0335-x · Cited by 137 · see citing works
Gómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112 · see citing works
Brinkmalm, G., Sjödin, S., Simonsen, A. H., Hasselbalch, S. G., Zetterberg, H., Brinkmalm, A., & Blennow, K. (2018) · PROTEOMICS – Clinical Applications · doi:10.1002/prca.201700131 · Cited by 111 · see citing works
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Figueiro-Silva, J., Gruart, A., Clayton, K. B., Podlesniy, P., Abad, M. A., Gasull, X., Delgado-García, J. M., & Trullas, R. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2548-14.2015 · Cited by 53 · see citing works
Self-citationKovács, R. Á., Vadászi, H., Bulyáki, É., Török, G., Tóth, V., Mátyás, D., Kun, J., Hunyadi-Gulyás, É., Fedor, F. Z., Csincsi, Á., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.599771 · Cited by 43 · see citing works
Clayton, K. B., Podlesniy, P., Figueiro-Silva, J., López-Doménech, G., Benitez, L., Enguita, M., Abad, M. A., Soriano, E., & Trullas, R. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4604-11.2012 · Cited by 28 · see citing works
Self-citationRajkumar, A. P., Christensen, J. H., Mattheisen, M., Jacobsen, I., Bache, I., Pallesen, J., Grove, J., Qvist, P., McQuillin, A., Gurling, H. M., et al. (2015) · Bipolar Disorders · doi:10.1111/bdi.12239 · Cited by 24 · see citing works
- Authors
- Abad, M. A., Enguita, M., DeGregorio-Rocasolano, N., Ferrer, I., & Trullas, R.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- ORCID
- Abad, Maria A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-12-06
- Volume
- 26
- Issue
- 49
- Pages
- 12735-12747
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6674827
- OpenAlex
- W2078165545
- Cited by
- 102
- References
- 51
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 12 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 10
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by-nc-sa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- amyloid-beta, Alzheimer's disease, neuronal apoptosis, synaptic loss, dystrophic neurites, tau protein, SNAP-25, APP/PS1 mice, cortical neurons, amyloid plaques
- MeSH terms
- Pentraxins, Aged, Alzheimer Disease, Animals, Brain, C-Reactive Protein, Cells, Cultured, Female, Gene Expression Regulation, Humans, Male, Mice, Transgenic, Nerve Tissue Proteins, Synapses, Up-Regulation, Amyloid beta-Peptides, Neurites, Rats, Sprague-Dawley, Mice, Rats
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