Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
Open accessAbstract
Considerable circumstantial evidence suggests that Abeta42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Abeta42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Abeta1-40 or Abeta1-42 in the absence of human amyloid beta protein precursor (APP) overexpression. Mice expressing high levels of Abeta1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Abeta1-42 accumulate insoluble Abeta1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Abeta deposits. When mice expressing Abeta1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Abeta1-42 is essential for amyloid deposition in the parenchyma and also in vessels.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
BRI-Aβ42 transgenic mice have established that Aβ42 is essential for parenchymal and vascular amyloid deposition.
“Recently, transgenic mice expressing a BRI protein-A 𝛃 42 fusion construct that generates only A 𝛃 42 in the brain have firmly established that A 𝛃 42 is essential for parenchymal and vascular amyloid deposition (McGowan et al., 2005).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as McGowan et al., 2005
Little evidence of intraneuronal Aβ was found in BRI-Aβ42 transgenic brain.
“In contrast to 5XFAD mice, little evidence of intraneuronal A 𝛃 was found in BRI-A 𝛃 42 transgenic brain.”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as McGowan et al., 2005
When Tg-BRI-Aβ42 Prp mice were crossed with Tg-swAPP Prp, the double transgenic mice had significantly increased RIPA-insoluble formic acid extracted Aβ40 and Aβ42 as well as enhanced amyloid deposition in several brain areas including BN compared with single transgenic Tg-swAPP Prp, Tg-BRI-Aβ40 Prp and BRI-Tg-Aβ42 Prp or Tg-swAPP Prp; Tg-BRI-Aβ40 Prp double transgenic littermates.
“In particular, when Tg-BRI-Ab42 Prp mice were crossed with Tg-swAPP Prp (53), the double transgenic Tg-swAPP Prp ; Tg-BRI-Ab42 Prp mice had significantly increased RIPA-insoluble formic acid extracted Ab40 and Ab42 as well as enhanced amyloid deposition in several brain areas including BN compared with single transgenic Tg-swAPP Prp”
From Amyloid precursor protein-induced axonopathies are independent of amyloid-β peptides (2008) · cites this paper as [45]
Fusions of BRI-Aβ42 chimeras lead to synthesis and secretion of Aβ42 and amyloid deposition.
“Previous work revealed that fusions of BRI-Ab42 chimeras lead to synthesis and secretion of Ab42 and amyloid deposition (45).”
From Amyloid precursor protein-induced axonopathies are independent of amyloid-β peptides (2008) · cites this paper as [45]
Aβ1-40 and Aβ42 have opposing effects on amyloid deposition in BRI2-Aβ transgenic mice crossed with Tg2576 mice.
“By crossing BRI2-A1-40 or BRI-A1-42 transgenic mice with Tg2576 mice, we previously demonstrated that A1-40 and A42 have opposing effects on amyloid deposition (McGowan et al., 2005;Kim et al., 2007).”
From BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008) · cites this paper as McGowan et al., 2005
The somatic brain transgenic BRI2-A1-40 studies confirmed previous studies using conventional transgenic mice expressing BRI2-A1-40.
“The studies with BRI2-A1-40 confirmed previous studies obtained using conventional transgenic mice expressing BRI2-A1-40 (McGowan et al., 2005;Kim et al., 2007).”
From BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008) · cites this paper as McGowan et al., 2005
Aβ42 is more neurotoxic and has a higher tendency to aggregate than Aβ40.
“Although Aβ40 is present in larger amounts in the brain, Aβ42 was found to be more neurotoxic and have a higher tendency to aggregate.4,5”
From The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity (2013) · cites this paper as [4]
The discrepancy in cognitive profiles between BRI2-Aβ and APP transgenic mice cannot be easily attributed to mouse genetic background, since genetic background is comparable between BRI2-Aβ and CRND8 models.
“This discrepancy in cognitive profiles between BRI2-Aβ and APP transgenic mice, for example APP CRND8 model tested intensively in our laboratory, cannot be easily attributed to the mouse genetic background, which is known to modulate behavior [35-37], since genetic background is comparable between BRI2-Aβ and CRND8 models [7,9].”
From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [7]
Both BRI2-Aβ1-40 and BRI2-Aβ1-42 mice show the presence of the respective soluble Aβ peptides at age 3 months at levels about 2- to 3-fold higher than levels of Aβ in 3- to 6-month-old APP Tg2576 mice.
“Both BRI2-Aβ1-40 and BRI2-Aβ1-42 mice show the presence of the respective soluble Aβ peptides at the age of 3 months at levels ~2- to 3-fold higher than the levels of Aβ in 3- to 6-month-old APP Tg2576 mice.”
From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [7]
Only BRI2-Aβ1-42 mice develop Aβ amyloid pathology in the brain at age 12 months with robust compact Aβ plaques in the hippocampus at 14 months.
“However, only BRI2-Aβ1-42 mice develop Aβ amyloid pathology in the brain at the age of 12 months with robust compact Aβ plaques in the hippocampus at 14 months [7].”
From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [7]
Aβ40 is present in larger amounts in the brain, yet Aβ42 is more neurotoxic and has a higher tendency to aggregate.
“Aβ40 is present in larger amounts in the brain, yet Aβ42 is more neurotoxic and has a higher tendency to aggregate.8–11”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide (2012) · cites this paper as [8]
The longer and more hydrophobic Aβ42 isoform has a higher tendency to generate neurotoxic oligomeric species than Aβ40.
“the longer and more hydrophobic Aβ42 isoform has a higher tendency to generate neurotoxic oligomeric species.9,10”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [9]
Aβ42 peptide is more prone to form neurotoxic soluble Aβ oligomers than the Aβ40 peptide.
“Although it was shown in previous studies9,10,21 that the Aβ42 peptide is more prone to form neurotoxic soluble Aβ oligomers than the Aβ40 peptide”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [9]
BRI-Aβ42A mice initially develop amyloid deposition in the cerebellum at ~3 months of age, whereas forebrain pathology is consistently observed only after ~12 months of age.
“BRI-A42A mice initially develop amyloid deposition in the cerebellum at ϳ3 months of age, whereas forebrain pathology was consistently observed only after ϳ12 months of age(McGowan et al., 2005).”
From Aβ40 Inhibits Amyloid Deposition<i>In Vivo</i> (2007) · cites this paper as McGowan et al., 2005
Aβ species, including the most abundant Aβ40 and more toxic Aβ42, are produced by two sequential proteolytic cleavages of amyloid precursor protein (APP) by β- and γ-secretases.
“Aβ species, including the most abundant Aβ40 and more toxic Aβ42, are produced by two sequential proteolytic cleavages of amyloid precursor protein (APP) by β- and γ-secretases (Kim et al., 2007; McGowan et al., 2005).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as McGowan et al., 2005
Several recent studies suggest that Aβ40 and Aβ42 may have opposing effects on Aβ aggregation in vivo.
“Several recent studies suggest that Aβ40 and Aβ42 may have opposing effects on Aβ aggregation in vivo (Kim et al., 2007; McGowan et al., 2005).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as McGowan et al., 2005
Emerging data from AD transgenic mice support that Aβ40 might even be protective against cerebral amyloid.
“Emerging data from AD transgenic mice support that Aβ40 might even be protective against cerebral amyloid [117].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [117]
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Self-citationAmyloid 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
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Self-citationPathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516 · see citing works
Jarrett, J. T., & Lansbury, P. T. (1993) · Cell · doi:10.1016/0092-8674(93)90635-4 · Cited by 2,178 · see citing works
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · see citing works
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Bürki, K., Frey, P., Paganetti, P. A., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13287 · Cited by 1,507 · see citing works
Holcomb, L., Gordon, M. N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., Wright, K., Saad, I., Mueller, R., Morgan, D., et al. (1998) · Nature Medicine · doi:10.1038/nm0198-097 · Cited by 1,386 · see citing works
Self-citationFarris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E., Frosch, M., Eckman, C., Tanzi, R., Selkoe, D., & Guénette, S. (2003) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0230450100 · Cited by 1,361 · see citing works
Self-citationKawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 3× · see citing works
“One BRI-Aβ1-40 founder had β40 plasma levels higher than levels seen in ageatched Tg2576 mice (Kawarabayashi et al., 2001), nd this line was also expanded.”
BackgroundMethodBorchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Calcium dyshomeostasis and intracellular signalling in alzheimer's disease
LaFerla, F. M. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn960 · Cited by 970 · see citing works
Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955 · see citing works
Holtzman, D. M., Bales, K. R., Tenkova, T., Fagan, A. M., Parsadanian, M., Sartorius, L. J., Mackey, B., Olney, J., McKeel, D., Wozniak, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050004797 · Cited by 937 · see citing works
Neurotoxicity of a Fragment of the Amyloid Precursor Associated with Alzheimer's Disease
Yankner, B. A., Dawes, L. R., Fisher, S., Villa-Komaroff, L., Oster-Granite, M. L., & Neve, R. L. (1989) · Science · doi:10.1126/science.2474201 · Cited by 907 · see citing works
The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease
Selkoe, D. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01363-4 · Cited by 862 · see citing works
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · cited 10× · see citing works
“The extensive Aβ42 deposition in the cerebellum and severe CAA in the BRI-Aβ42 mice mimics the pattern of amyloid deposition seen in FBD (Ghiso et al., 2000; Holton et al., 2001; Vidal et al., 1999).”
BackgroundInfluentialSelf-citationOhno, M., Sametsky, E. A., Younkin, L. H., Oakley, H., Younkin, S. G., Citron, M., Vassar, R., & Disterhoft, J. F. (2004) · Neuron · doi:10.1016/s0896-6273(03)00810-9 · Cited by 549 · see citing works
The Alzheimer's Aβ peptide induces neurodegeneration and apoptotic cell death in transgenic mice
LaFerla, F. M., Tinkle, B. T., Bieberich, C. J., Haudenschild, C. C., & Jay, G. (1995) · Nature Genetics · doi:10.1038/ng0195-21 · Cited by 513 · see citing works
Bales, K. R., Verina, T., Cummins, D. J., Du, Y., Dodel, R. C., Saura, J., Fishman, C. E., DeLong, C. A., Piccardo, P., Petegnief, V., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15233 · Cited by 486 · see citing works
Iijima, K., Liu, H., Chiang, A., Hearn, S., Konsolaki, M., & Zhong, Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400895101 · Cited by 482 · see citing works
A stop-codon mutation in the BRI gene associated with familial British dementia
Vidal, R., Frangione, B., Rostagno, A., Mead, S., Révész, T., Plant, G., & Ghiso, J. (1999) · Nature · doi:10.1038/21637 · Cited by 466 · see citing works
Zhang, Y., McLaughlin, R., Goodyer, C., & LeBlanc, A. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110119 · Cited by 418 · see citing works
ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Price, D. L., Tanzi, R. E., Borchelt, D. R., & Sisodia, S. S. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.461 · Cited by 406 · see citing works
A second cytotoxic proteolytic peptide derived from amyloid β-protein precursor
Lu, D. C.-T., Rabizadeh, S., Chandra, S. S., Shayya, R. F., Ellerby, L., Ye, X., Salvesen, G. S., Koo, E. H., & Bredesen, D. E. (2000) · Nature Medicine · doi:10.1038/74656 · Cited by 395 · 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
A vector for expressing foreign genes in the brains and hearts of transgenic mice
Borchelt, D., Davis, J. A., Fischer, M., Lee, M. K., Slunt, H. H., Ratovitski, T., Regard, J. B., Copeland, N. G., Jenkins, N. A., Sisodia, S. S., et al. (1996) · Genetic Analysis Biomolecular Engineering · doi:10.1016/s1050-3862(96)00167-2 · Cited by 362 · see citing works
Golde, T. E., Eckman, C. B., & Younkin, S. G. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00043-0 · Cited by 300 · see citing works
Self-citationVidal, R., Révész, T., Rostagno, A., Kim, E., Holton, J. L., Bek, T., Bojsen-Møller, M., Braendgaard, H., Plant, G., Ghiso, J., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.080076097 · Cited by 300 · see citing works
The Profile of Soluble Amyloid β Protein in Cultured Cell Media
Wang, R., Sweeney, D. A., Gandy, S., & Sisodia, S. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.31894 · Cited by 293 · see citing works
Self-citationThe role of Aβ42 in Alzheimer's disease
Younkin, S. G. (1998) · Journal of Physiology-Paris · doi:10.1016/s0928-4257(98)80035-1 · Cited by 282 · see citing works
Interaction between Aβ(1−42) and Aβ(1−40) in Alzheimer's β-Amyloid Fibril Formation in Vitro
Hasegawa, K., Yamaguchi, I., Omata, S., Gejyo, F., & Naiki, H. (1999) · Biochemistry · doi:10.1021/bi991161m · Cited by 217 · see citing works
Holton, J. L., Ghiso, J. A., Lashley, T., Rostagno, A. A., Guérin, C. J., Gibb, G., Houlden, H., Ayling, H., Martinian, L., Anderton, B. H., et al. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63993-4 · Cited by 131 · see citing works
Interaction of human and mouse Aβ peptides
Fung, J., Frost, D. W., Chakrabartty, A., & McLaurin, J. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02828.x · Cited by 49 · see citing works
Pype, S., Moechars, D., Dillen, L., & Mercken, M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01556.x · Cited by 47 · see citing works
Lewis, P. A., Piper, S. C., Baker, M., Onstead, L., Murphy, M. P., Hardy, J., Wang, R., McGowan, E. M., & Golde, T. E. (2001) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(01)00054-0 · Cited by 42 · see citing works
Self-citationAmyloidogenesis in Familial British Dementia Is Associated with a Genetic Defect on Chromosome 13
Ghiso, J. A., Vidal, R., Rostagno, A. A., Miravalle, L., Holton, J. L., Mead, S., Révész, T., Plant, G. T., & Frangione, B. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06908.x · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · 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
“Recently, transgenic mice expressing a BRI protein–A 42 fusion construct that generates only A 42 in the brain have firmly established that A 42 is essential for parenchymal and vascular amyloid deposition (McGowan et al., 2005).”
BackgroundThe role of apolipoprotein E in Alzheimer's disease
Kim, J., Basak, J. M., & Holtzman, D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.026 · Cited by 1,661 · see citing works
Self-citationSpilman, P., Podlutskaya, N., Hart, M. J., Debnath, J., Gorostiza, O., Bredesen, D., Richardson, A., Strong, R., & Galvan, V. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009979 · Cited by 1,033 · see citing works
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
Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947 · see citing works
Animal models of neurodegenerative diseases
Dawson, T. M., Golde, T. E., & Lagier-Tourenne, C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0236-8 · Cited by 576 · see citing works
Self-citationCurrent state of Alzheimer’s fluid biomarkers
Molinuevo, J. L., Ayton, S., Batrla, R., Bednar, M. M., Bittner, T., Cummings, J., Fagan, A. M., Hampel, H., Mielke, M. M., Mikulskis, A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1932-x · Cited by 518 · see citing works
REVIEW: Curcumin and Alzheimer’s disease
Hamaguchi, T., Ono, K., & Yamada, M. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00147.x · Cited by 450 · see citing works
Animal Models of Alzheimer Disease
LaFerla, F. M., & Green, K. N. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006320 · Cited by 419 · see citing works
Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372 · see citing works
Aβ40 Inhibits Amyloid Deposition<i>In Vivo</i>
Kim, J., Onstead, L., Randle, S., Price, R., Smithson, L., Zwizinski, C., Dickson, D. W., Golde, T., & McGowan, E. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4849-06.2007 · Cited by 359 · see citing works
“BRI-A 42A mice led to a reduction in CAA, demonstrating that A 40 has anti-amyloidogenic effects on not only parenchymal but also vascular amyloid deposition.”
BackgroundMethodInfluentialSelf-citationTransgenic mouse models of Alzheimer’s disease.
Elder, G. A., Gama Sosa, M. A., & De Gasperi, R. (2010) · Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20159 · Cited by 336 · see citing works
Jan, A., Gokce, O., Luthi-Carter, R., & Lashuel, H. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803159200 · Cited by 291 · see citing works
Brain levels of sex steroid hormones in men and women during normal aging and in Alzheimer's disease
Rosario, E. R., Chang, L., Head, E. H., Stanczyk, F. Z., & Pike, C. J. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.04.008 · Cited by 289 · see citing works
Lessons from a failed γ-secretase Alzheimer trial
De Strooper, B. (2014) · Cell · doi:10.1016/j.cell.2014.10.016 · Cited by 277 · see citing works
Role of tau protein in Alzheimer’s disease: The prime pathological player
Muralidar, S., Ambi, S. V., Sekaran, S., Thirumalai, D., & Palaniappan, B. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.07.327 · Cited by 278 · see citing works
Ahmed, Z., Shaw, G., Sharma, V. P., Yang, C., McGowan, E., & Dickson, D. W. (2007) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.6a7156.2007 · Cited by 258 · see citing works
Self-citationOn the Seeding and Oligomerization of pGlu-Amyloid Peptides (<i>in vitro</i>)
Schilling, S., Lauber, T., Schaupp, M., Manhart, S., Scheel, E., Böhm, G., & Demuth, H.-U. (2006) · Biochemistry · doi:10.1021/bi0612667 · Cited by 254 · 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
Pyroglutamate Formation Influences Solubility and Amyloidogenicity of Amyloid Peptides
Schlenzig, D., Manhart, S., Cinar, Y., Kleinschmidt, M., Hause, G., Willbold, D., Funke, S. A., Schilling, S., & Demuth, H.-U. (2009) · Biochemistry · doi:10.1021/bi900818a · Cited by 228 · see citing works
Sun, B., Halabisky, B., Zhou, Y., Palop, J. J., Yu, G., Mucke, L., & Gan, L. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.10.003 · Cited by 205 · see citing works
Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ<sub>42</sub>Peptide
Sharma, A. K., Pavlova, S. T., Kim, J., Finkelstein, D., Hawco, N. J., Rath, N. P., Kim, J., & Mirica, L. M. (2012) · Journal of the American Chemical Society · doi:10.1021/ja210588m · Cited by 202 · see citing works
Self-citationNeurovascular Dysfunction in Vascular Dementia, Alzheimer's and Atherosclerosis
Shabir, O., Berwick, J., & Francis, S. E. (2018) · BMC Neuroscience · doi:10.1186/s12868-018-0465-5 · Cited by 191 · see citing works
The Alzheimer’s Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease
Stakos, D. A., Stamatelopoulos, K., Bampatsias, D., Sachse, M., Zormpas, E., Vlachogiannis, N. I., Tual-Chalot, S., & Stellos, K. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.12.033 · Cited by 188 · see citing works
Fukui, H., Diaz, F., Garcia, S., & Moraes, C. T. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705738104 · Cited by 185 · see citing works
A <i>β</i> 42 and A <i>β</i> 40: similarities and differences
Qiu, T., Liu, Q., Chen, Y., Zhao, Y., & Li, Y. (2015) · Journal of Peptide Science · doi:10.1002/psc.2789 · Cited by 180 · see citing works
miR-106b impairs cholesterol efflux and increases Aβ levels by repressing ABCA1 expression
Kim, J., Yoon, H., Ramírez, C. M., Lee, S.-M., Hoe, H.-S., Fernández-Hernando, C., & Kim, J. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.11.010 · Cited by 173 · see citing works
Self-citationMore than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration
Lane-Donovan, C., Philips, G. T., & Herz, J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.005 · Cited by 158 · see citing works
Insulin Receptor Dysfunction Impairs Cellular Clearance of Neurotoxic Oligomeric Aβ
Zhao, W.-Q., Lacor, P. N., Chen, H., Lambert, M. P., Quon, M. J., Krafft, G. A., & Klein, W. L. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.011015 · Cited by 154 · see citing works
Tauopathy with paired helical filaments in an aged chimpanzee
Rosen, R. F., Farberg, A. S., Gearing, M., Dooyema, J., M. Long, P., Anderson, D. C., Davis‐Turak, J., Coppola, G., Geschwind, D. H., Paré, J., et al. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21744 · Cited by 153 · see citing works
Kwak, S. S., Washicosky, K. J., Brand, E., von Maydell, D., Aronson, J., Kim, S., Capen, D. E., Cetinbas, M., Sadreyev, R., Ning, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15120-3 · Cited by 151 · see citing works
Kim, J., Yoon, H., Basak, J., & Kim, J. (2014) · Molecules and Cells · doi:10.14348/molcells.2014.0248 · Cited by 141 · see citing works
“A species, including the most abundant A40 and more toxic A42, are produced by two sequential proteolytic cleavages of amyloid precursor protein (APP) by and γ-secretases (Kim et al., 2007; McGowan et al., 2005).”
BackgroundSelf-citationThe effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity
Sharma, A. K., Pavlova, S. T., Kim, J., Kim, J., & Mirica, L. M. (2013) · Metallomics · doi:10.1039/c3mt00161j · Cited by 135 · see citing works
Self-citationThal, D. R., Griffin, W. S. T., & Braak, H. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00411.x · Cited by 134 · see citing works
Devi, L., Alldred, M. J., Ginsberg, S. D., & Ohno, M. (2010) · Molecular Brain · doi:10.1186/1756-6606-3-34 · Cited by 129 · see citing works
Disease-Modifying Therapies for Alzheimer’s Disease: More Questions than Answers
Golde, T. E. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01201-2 · Cited by 119 · see citing works
Self-citationZhang, Y., Rempel, D. L., Zhang, J., Sharma, A. K., Mirica, L. M., & Gross, M. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1309175110 · Cited by 118 · see citing works
BRI2 (ITM2b) Inhibits A Deposition In Vivo
Kim, J., Miller, V. M., Levites, Y., West, K. J., Zwizinski, C. W., Moore, B. D., Troendle, F. J., Bann, M., Verbeeck, C., Price, R. W., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0891-08.2008 · Cited by 113 · see citing works
Self-citationDistinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.906 · Cited by 104 · see citing works
Alexandru, A., Jagla, W., Graubner, S., Becker, A., Bäuscher, C., Kohlmann, S., Sedlmeier, R., Raber, K. A., Cynis, H., Rönicke, R., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1794-11.2011 · Cited by 102 · see citing works
miR‐186 is decreased in aged brain and suppresses <scp>BACE</scp>1 expression
Kim, J., Yoon, H., Chung, D., Brown, J. L., Belmonte, K. C., & Kim, J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13507 · Cited by 102 · see citing works
“After transferring, membranes were boiled for 10 min in phosphate-buffered saline, as previously reported (McGowan et al. 2005).”
MethodSelf-citationCognitive impairment in humanized APP×PS1 mice is linked to Aβ1–42 and NOX activation
Bruce-Keller, A. J., Gupta, S., Knight, A. G., Beckett, T. L., McMullen, J. M., Davis, P. R., Murphy, M. P., Van Eldik, L. J., St Clair, D., & Keller, J. N. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.07.012 · Cited by 96 · see citing works
Targeting Aβ and tau in Alzheimer's disease, an early interim report
Golde, T. E., Petrucelli, L., & Lewis, J. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2009.07.035 · Cited by 89 · see citing works
Self-citation(2012) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-385883-2.00006-0 · Cited by 84 · see citing works
Normal cognition in transgenic BRI2-Aβ mice
Kim, J., Chakrabarty, P., Hanna, A., March, A., Dickson, D. W., Borchelt, D. R., Golde, T., & Janus, C. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-15 · Cited by 83 · see citing works
Self-citationImaging of cerebrovascular pathology in animal models of Alzheimer's disease
Klohs, J., Rudin, M., Shimshek, D. R., & Beckmann, N. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00032 · Cited by 82 · see citing works
Liao, F., Zhang, T. J., Jiang, H., Lefton, K. B., Robinson, G. O., Vassar, R., Sullivan, P. M., & Holtzman, D. M. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0250-y · Cited by 77 · see citing works
Amyloid precursor protein-induced axonopathies are independent of amyloid-β peptides
Stokin, G. B., Almenar-Queralt, A., Gunawardena, S., Rodrigues, E. M., Falzone, T., Kim, J., Lillo, C., Mount, S. L., Roberts, E. A., McGowan, E., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn240 · Cited by 72 · see citing works
Self-citationFuentealba, R. A., Barría, M. I., Lee, J., Cam, J., Araya, C., Escudero, C. A., Inestrosa, N. C., Bronfman, F. C., Bu, G., & Marzolo, M.-P. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-14 · Cited by 70 · 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
Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease
Hullinger, R., & Puglielli, L. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.008 · Cited by 68 · see citing works
Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits
Xu, G., Ran, Y., Fromholt, S. E., Fu, C., Yachnis, A. T., Golde, T. E., & Borchelt, D. R. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0252-9 · Cited by 65 · see citing works
Self-citationγ-Secretase and its modulators: Twenty years and beyond
Xia, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.02.011 · Cited by 54 · see citing works
Modulation of the Aβ peptide aggregation pathway by KP1019 limits Aβ-associated neurotoxicity
Jones, M. R., Mu, C., Wang, M. C. P., Webb, M. I., Walsby, C. J., & Storr, T. (2015) · Metallomics · doi:10.1039/c4mt00252k · Cited by 50 · see citing works
Sharma, A. K., Kim, J., Prior, J. T., Hawco, N. J., Rath, N. P., Kim, J., & Mirica, L. M. (2014) · Inorganic Chemistry · doi:10.1021/ic500926c · Cited by 48 · see citing works
Self-citationComparative pathobiology of β-amyloid and the unique susceptibility of humans to Alzheimer's disease
Rosen, R. F., Tomidokoro, Y., Farberg, A. S., Dooyema, J., Ciliax, B., Preuss, T. M., Neubert, T. A., Ghiso, J. A., LeVine, H., & Walker, L. C. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.019 · Cited by 46 · 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
Tambini, M. D., Yao, W., & D'Adamio, L. (2019) · Aging Cell · doi:10.1111/acel.13033 · Cited by 40 · see citing works
He, P., Staufenbiel, M., Li, R., & Shen, Y. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu370 · Cited by 33 · see citing works
Human APOE genotype affects intraneuronal A 1-42 accumulation in a lentiviral gene transfer model
Zhao, W., Dumanis, S. B., Tamboli, I. Y., Rodriguez, G. A., Jo LaDu, M., Moussa, C. E. H., & William Rebeck, G. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt525 · Cited by 32 · see citing works
The roles of GxxxG motif and gamma-secretase components in APP processing
Kim, J. (2009) · Interdisciplinary Bio Central · doi:10.4051/ibc.2009.4.0015 · Cited by 3 · see citing works
Self-citation
- Authors
- McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., Jansen, K., DeLucia, M., Lin, W.-L., Dolios, G., Wang, R., Eckman, C. B., Dickson, D. W., Hutton, M., Hardy, J., & Golde, T.
- Affiliations
- Mayo Clinic (US)
- Icahn School of Medicine at Mount Sinai (US)
- National Institutes of Health (US)
- Corresponding author
- McGowan, Eileen
- Golde, Todd
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 47
- Issue
- 2
- Pages
- 191-199
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC1373682
- OpenAlex
- W2020824841
- Cited by
- 565
- References
- 40
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 14 · 2023: 17 · 2022: 18 · 2021: 22 · 2020: 40 · 2019: 19 · 2018: 23 · 2017: 27 · 2016: 23 · 2015: 21 · 2014: 29 · 2013: 42 · 2012: 30
- FWCI
- 20.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2938 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- Mayo Clinic
- Mayo Foundation for Medical Education and Research
- Chinese Academy of Agricultural Sciences
- National Institute on Aging (R01AG022595)
- National Cancer Institute (CA88325, R24 CA088325)
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta 42, Aβ40, Alzheimer's disease, amyloid deposition, amyloid plaques, vascular amyloid, APP, Tg2576 mice, transgenic mice, amyloid precursor protein
- MeSH terms
- Age Factors, Animals, Blood Vessels, Brain, Enzyme-Linked Immunosorbent Assay, Female, Glial Fibrillary Acidic Protein, Humans, Immunohistochemistry, Male, Mice, Transgenic, Mutation, Peptide Fragments, Pia Mater, Mass Spectrometry, Thiazoles, Blotting, Northern, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cerebral Amyloid Angiopathy, In Situ Hybridization, Microscopy, Electron, Transmission, Immunoprecipitation, Mice, Benzothiazoles, 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
