Aβ-induced acceleration of Alzheimer-related τ-pathology spreading and its association with prion protein
Open accessAbstract
Extracellular deposition of amyloid β-protein (Aβ) in amyloid plaques and intracellular accumulation of abnormally phosphorylated τ-protein (p-τ) in neurofibrillary tangles (NFTs) represent pathological hallmark lesions of Alzheimer's disease (AD). Both lesions develop in parallel in the human brain throughout the preclinical and clinical course of AD. Nevertheless, it is not yet clear whether there is a direct link between Aβ and τ pathology or whether other proteins are involved in this process. To address this question, we crossed amyloid precursor protein (APP) transgenic mice overexpressing human APP with the Swedish mutation (670/671 KM → NL) (APP23), human wild-type APP (APP51/16), or a proenkephalin signal peptide linked to human Aβ 42 (APP48) with τ-transgenic mice overexpressing human mutant 4-repeat τ-protein with the P301S mutation (TAU58). In 6-month-old APP23xTAU58 and APP51/16xTAU58 mice, soluble Aβ was associated with the aggravation of p-τ pathology propagation into the CA1/subiculum region, whereas 6-month-old TAU58 and APP48xTAU58 mice neither exhibited significant amounts of p-τ pathology in the CA1/subiculum region nor displayed significant levels of soluble Aβ in the forebrain. In APP23xTAU58 and APP51/16xTAU58 mice showing an acceleration of p-τ propagation, Aβ and p-τ were co-immunoprecipitated with cellular prion protein (PrP C ). A similar interaction between PrP C , p-τ and Aβ was observed in human AD brains. This association was particularly notice…
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Double transgenic APP48/TAU58 mice showed neither evidence of increased levels of soluble Aβ, albeit data on Aβ levels in single transgenic APP48 mice were not reported, nor significant amounts of phospho-tau pathology.
“Double transgenic mice showed neither evidence of increased levels of soluble Aβ, albeit data on Aβ levels in single transgenic APP48 mice were not reported, nor significant amounts of phospho-tau pathology [20].”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [20]
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064 · see citing works
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172 · see citing works
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
Self-citationNeurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668 · see citing works
Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419 · see citing works
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Self-citationCellular 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 · see citing works
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870 · see citing works
The pathological process underlying Alzheimer’s disease in individuals under thirty
Braak, H., & Del Tredici, K. (2011) · Acta Neuropathologica · doi:10.1007/s00401-010-0789-4 · Cited by 812 · see citing works
He, Z., Guo, J. L., McBride, J. D., Narasimhan, S., Kim, H., Changolkar, L., Zhang, B., Gathagan, R. J., Yue, C., Dengler, C., et al. (2018) · Nature Medicine · doi:10.1038/nm.4443 · Cited by 645 · see citing works
Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders
Jucker, M., & Walker, L. C. (2011) · Annals of Neurology · doi:10.1002/ana.22615 · Cited by 622 · see citing works
Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M. (1994) · Journal of Neuroscience Research · doi:10.1002/jnr.490390607 · Cited by 488 · see citing works
Synthetic 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 · see citing works
Herzig, M. C., Winkler, D. T., Burgermeister, P., Pfeifer, M., Kohler, E., Schmidt, S. D., Danner, S., Abramowski, D., Stürchler-Pierrat, C., Bürki, K., et al. (2004) · Nature Neuroscience · doi:10.1038/nn1302 · Cited by 391 · see citing works
Self-citationTau Aggregation and Its Interplay with Amyloid-β
Nisbet, R. M., Polanco, J.-C., Ittner, L. M., & Götz, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-014-1371-2 · Cited by 359 · see citing works
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 · see citing works
The Development of Amyloid β Protein Deposits in the Aged Brain
Thal, D. R., Capetillo-Zarate, E., Del Tredici, K., & Braak, H. (2006) · Science of Aging Knowledge Environment · doi:10.1126/sageke.2006.6.re1 · Cited by 234 · see citing works
Self-citationHurtado, D. E., Molina-Porcel, L., Iba, M., Aboagye, A. K., Paul, S. M., Trojanowski, J. Q., & Lee, V. M.-Y. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100346 · Cited by 222 · 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
Abramowski, D., Rabe, S., Upadhaya, A. R., Reichwald, J., Danner, S., Staab, D., Capetillo-Zarate, E., Yamaguchi, H., Saido, T. C., Wiederhold, K.-H., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4586-11.2012 · Cited by 41 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Synergy between amyloid-β and tau in Alzheimer’s disease
Busche, M. A., & Hyman, B. T. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0687-6 · Cited by 1,242 · see citing works
Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.57078 · Cited by 689 · see citing works
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625 · see citing works
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 · see citing works
Self-citationAmyloid-beta peptide and tau protein crosstalk in Alzheimer’s disease
Villegas, S., Roda, A., Serra-Mir, G., Montoliu-Gaya, L., & Tiessler, L. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.332127 · Cited by 306 · see citing works
Ciccone, L., Shi, C., di Lorenzo, D., Van Baelen, A.-C., & Tonali, N. (2020) · Molecules · doi:10.3390/molecules25102439 · Cited by 69 · see citing works
Vanderlinden, G., Ceccarini, J., Vande Casteele, T., Michiels, L., Lemmens, R., Triau, E., Serdons, K., Tournoy, J., Koole, M., Vandenbulcke, M., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01672-x · Cited by 47 · see citing works
Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease
Li, X., Tsolis, K. C., Koper, M. J., Ronisz, A., Ospitalieri, S., von Arnim, C. A. F., Vandenberghe, R., Tousseyn, T., Scheuerle, A., Economou, A., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12345 · Cited by 27 · see citing works
Self-citationCharacterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau
Zampar, S., & Wirths, O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105191 · Cited by 18 · see citing works
“Double transgenic mice showed neither evidence of increased levels of soluble Aβ, albeit data on Aβ levels in single transgenic APP48 mice were not reported, nor significant amounts of phospho-tau pathology [20].”
BackgroundMoszczynski, A. J., Harvey, M., Fulcher, N., de Oliveira, C., McCunn, P., Donison, N., Bartha, R., Schmid, S., Strong, M. J., & Volkening, K. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0816-1 · Cited by 15 · see citing works
- Authors
- Gomes, L. A., Hipp, S. A., Rijal Upadhaya, A., Balakrishnan, K., Ospitalieri, S., Koper, M. J., Largo-Barrientos, P., Uytterhoeven, V., Reichwald, J., Rabe, S., Vandenberghe, R., von Arnim, C. A. F., Tousseyn, T., Feederle, R., Giudici, C., Willem, M., Staufenbiel, M., & Thal, D. R.
- Affiliations
- KU Leuven (BE)
- Universität Ulm (DE)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- Novartis (Switzerland) (CH)
- Universitair Ziekenhuis Leuven (BE)
- German Center for Neurodegenerative Diseases (DE)
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Thal, Dietmar Rudolf
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2019-08-14
- Volume
- 138
- Issue
- 6
- Pages
- 913-941
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2967399997
- Cited by
- 125
- References
- 22
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 18 · 2023: 11 · 2022: 16 · 2021: 30 · 2020: 19 · 2019: 5 · 2013: 1
- FWCI
- 11.96
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- The Novartis Repository (Novartis) (submittedVersion)
- Site cant be reached (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek (G0F8516N)
- Alzheimer Forschung Initiative (#10810)
- Vlaamse Overheid (IWT 135043)
- 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, amyloid-beta, tau phosphorylation, neurofibrillary tangles, amyloid plaques, cellular prion protein, prion-like propagation, APP transgenic mice, protein-protein interaction, disease progression, proximity ligation assay, immunoprecipitation
- MeSH terms
- Prion Proteins, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Mice, Transgenic, Mutation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Plaque, Amyloid
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