Presenilin-1 P264L Knock-In Mutation: Differential Effects on Aβ Production, Amyloid Deposition, and Neuronal Vulnerability

Siman, Robert; Reaume, Andrew G.; Savage, Mary J.; Trusko, Stephen; Lin, Yin-Guo; Scott, Richard W.; Flood, Dorothy G.

doi:10.1523/jneurosci.20-23-08717.2000

Cited by 133Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Presenilin-1 P264L Knock-In Mutation: Differential Effects on Aβ Production, Amyloid Deposition, and Neuronal Vulnerability

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Siman, Robert, Reaume, Andrew G., Savage, Mary J., Trusko, Stephen, Lin, Yin-Guo, Scott, Richard W., Flood, Dorothy G.·2000·The Journal of Neuroscience

DOI 10.1523/jneurosci.20-23-08717.2000PMC PMC6773081

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Abstract

The pathogenic mechanism linking presenilin-1 (PS-1) gene mutations to familial Alzheimer's disease (FAD) is uncertain, but has been proposed to include increased neuronal sensitivity to degeneration and enhanced amyloidogenic processing of the β-amyloid precursor protein (APP). We investigated this issue by using gene targeting with the Cre-lox system to introduce an FAD-linked P264L mutation into the endogenous mouse PS-1 gene, an approach that maintains normal regulatory controls over expression. Primary cortical neurons derived from PS-1 homozygous mutant knock-in mice exhibit basal neurodegeneration similar to their PS-1 wild-type counterparts. Staurosporine and Aβ1–42 induce apoptosis, and neither the dose dependence nor maximal extent of cell death is altered by the PS-1 knock-in mutation. Similarly, glutamate-induced neuronal necrosis is unaffected by the PS-1P264L mutation. The lack of effect of the PS-1P264L mutation is confirmed by measures of basal- and toxin-induced caspase and calpain activation, biochemical indices of apoptotic and necrotic signaling, respectively. To analyze the influence of the PS-1P264L knock-in mutation on APP processing and the development of AD-type neuropathology, we created mouse lines carrying mutations in both PS-1 and APP. In contrast to the lack of effect on neuronal vulnerability, cortical neurons cultured from PS-1P264L homozygous mutant mice secrete Aβ42 at an increased rate, whereas secretion of Aβ40 is reduced. Moreover, the PS-1 knock-in mutation selectively increases Aβ42 levels in the mouse brain and accelerates the onset of amyloid deposition and its attendant reactive gliosis, even as a single mutant allele. We conclude that expression of an FAD-linked mutant PS-1 at normal levels does not generally increase cortical neuronal sensitivity to degeneration. Instead, enhanced amyloidogenic processing of APP likely is critical to the pathogenesis of PS-1-linked FAD.

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FAD mutations can even decrease secretion of the most abundantly released Aβ isoform, Aβ40, while still increasing the Aβ42 to Aβ40 ratio.
“FAD mutations can even decrease secretion of the most abundantly released Aβ isoform, Aβ40, while still increasing the Aβ42 to Aβ40 ratio [90, 134, 173].”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [173]

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Caspases: Enemies Within
Thornberry, N. A., & Lazebnik, Y. A. (1998) · Science · doi:10.1126/science.281.5381.1312 · Cited by 6,857 · 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
Diffusible, nonfibrillar ligands derived from Aβ <sub>1–42</sub> are potent central nervous system neurotoxins
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
Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · 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
A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain
De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., et al. (1999) · Nature · doi:10.1038/19083 · Cited by 2,100 · see citing works
Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity
Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., & Selkoe, D. J. (1999) · Nature · doi:10.1038/19077 · Cited by 1,913 · see citing works
Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., & Van Leuven, F. (1998) · Nature · doi:10.1038/34910 · Cited by 1,818 · see citing works
Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production
Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757 · 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
Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo
Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80230-5 · Cited by 1,478 · see citing works
An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp <sub>717</sub> ) Mutants
Suzuki, N., Cheung, T. T., Cai, X.-D., Odaka, A., Otvos, L., Eckman, C., Golde, T. E., & Younkin, S. G. (1994) · Science · doi:10.1126/science.8191290 · Cited by 1,471 · see citing works
Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,453 · see citing works
Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes
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
Amyloid, the presenilins and Alzheimer’s disease
Hardy, J. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01030-2 · Cited by 1,370 · see citing works
Culturing nerve cells
Banker, G. A., & Goslin, K. (1998) · Cited by 1,290 · see citing works
Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271 · see citing works
Accelerated Amyloid Deposition in the Brains of Transgenic Mice Coexpressing Mutant Presenilin 1 and Amyloid Precursor Proteins
Borchelt, 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
Endoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives In Vivo
Thinakaran, G., Borchelt, D., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G. J., Ratovitski, T., Davenport, F., Nordstedt, C., Seeger, M., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80291-3 · Cited by 1,009 · see citing works
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991 · see citing works
Protofibrillar Intermediates of Amyloid β-Protein Induce Acute Electrophysiological Changes and Progressive Neurotoxicity in Cortical Neurons
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
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 947 · see citing works
Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein Precursor
Cai, X.-D., Golde, T. E., & Younkin, S. G. (1993) · Science · doi:10.1126/science.8424174 · Cited by 913 · see citing works
Calpain and caspase: can you tell the difference?
Wang, K. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01479-4 · Cited by 912 · 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
Distinct sites of intracellular production for Alzheimer's disease Aβ40/42 amyloid peptides
Hartmann, T., Bieger, S. C., Brühl, B., Tienari, P. J., Ida, N., Allsop, D., Roberts, G. W., Masters, C. L., Dotti, C. G., Unsicker, K., et al. (1997) · Nature Medicine · doi:10.1038/nm0997-1016 · Cited by 706 · see citing works
Microglial response to amyloid plaques in APPsw transgenic mice.
Frautschy, S. A., Yang, F., Irrizarry, M., Hyman, B. T., Saido, T. C., Hsiao, K., & Cole, G. M. (1998) · Europe PMC (PubMed Central) · Cited by 592 · see citing works
Alzheimer–associated presenilins 1 and 2 : Neuronal expression in brain and localization to intracellular membranes in mammalian cells
Kovacs, D. M., Fausett, H. J., Page, K. J., Kim, T., Moir, R. D., Merriam, D. E., Hollister, R. D., Hallmark, O. G., Mancini, R., Felsenstein, K. M., et al. (1996) · Nature Medicine · doi:10.1038/nm0296-224 · Cited by 551 · see citing works
Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response
Katayama, T., Imaizumi, K., Sato, N., Miyoshi, K., Kudo, T., Hitomi, J., Morihara, T., Yoneda, T., Gomi, F., Mori, Y., et al. (1999) · Nature Cell Biology · doi:10.1038/70265 · Cited by 521 · see citing works
Destabilization of β-catenin by mutations in presenilin-1 potentiates neuronal apoptosis
Zhang, Z., Hartmann, H., Do, V. M., Abramowski, D., Sturchler, C., Staufenbiel, M., Sommer, B., van de Wetering, M., Clevers, H. C., Säftig, P., et al. (1998) · Nature · doi:10.1038/27208 · Cited by 511 · see citing works
Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice
Guo, Q., Fu, W., Sopher, B. L., Miller, M. W., Ware, C. B., Martin, G. M., & Mattson, M. P. (1999) · Nature Medicine · doi:10.1038/4789 · Cited by 489 · see citing works
Alzheimer's Aβ(1–42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells
Cook, D. G., Forman, M. S., Sung, J. C., Leight, S., Kolson, D. L., Iwatsubo, T., Lee, V. M.-Y., & Doms, R. W. (1997) · Nature Medicine · doi:10.1038/nm0997-1021 · Cited by 439 · see citing works
Excitatory amino acids activate calpain I and induce structural protein breakdown in vivo
Siman, R. G., & Noszek, J. C. (1988) · Neuron · doi:10.1016/0896-6273(88)90076-1 · Cited by 434 · see citing works
Self-citation
Participation of Presenilin 2 in Apoptosis: Enhanced Basal Activity Conferred by an Alzheimer Mutation
Wolozin, B. L., Iwasaki, K., Vito, P., Ganjei, J. K., Lacaná, E., Sunderland, T., Zhao, B., Kusiak, J. W., Wasco, W., & D'adamio, L. (1996) · Science · doi:10.1126/science.274.5293.1710 · Cited by 421 · 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
Constitutive expression of the machinery for programmed cell death.
Weil, M., Jacobson, M. D., Coles, H., Davies, T. J., Gardner, R. L., Raff, K., & RAFF, M. C. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.133.5.1053 · Cited by 383 · see citing works
Protein Topology of Presenilin 1
Doan, A., Thinakaran, G., Borchelt, D., Slunt, H. H., Ratovitski, T., Podlisny, M. B., Selkoe, D. J., Seeger, M., Gandy, S., Price, D. L., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80232-9 · Cited by 371 · see citing works
Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer β-amyloid peptides
Greenfield, J. P., Tsai, J., Gouras, G. K., Hai, B., Thinakaran, G., Checler, F., Sisodia, S. S., Greengard, P., & Xu, H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.2.742 · Cited by 366 · see citing works
Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation
Chui, D.-H., Tanahashi, H., Ozawa, K., Ikeda, S., Checler, F., Ueda, O., Suzuki, H., Araki, W., Inoue, H., Shirotani, K., et al. (1999) · Nature Medicine · doi:10.1038/8438 · Cited by 364 · see citing works
Assessment of normal and mutant human presenilin function in Caenorhabditis elegans
Levitan, D. J., Doyle, T. G., Brousseau, D., Lee, M. K., Thinakaran, G., Slunt, H. H., Sisodia, S. S., & Greenwald, I. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14940 · Cited by 354 · see citing works
Clinical Features of Early-Onset Alzheimer Disease in a Large Kindred With an E280A Presenilin-1 Mutation
Lopera, F. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340027028 · Cited by 351 · see citing works
Biosynthesis of an Endogenous Cannabinoid Precursor in Neurons and its Control by Calcium and cAMP
Cadas, H., Gaillet, S., Beltramo, M., Venance, L., & Piomelli, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-12-03934.1996 · Cited by 318 · see citing works
Immunolocalization of calpain I-mediated spectrin degradation to vulnerable neurons in the ischemic gerbil brain
Roberts‐Lewis, J. M., Mj, S., Marcy, V. R., Pinsker, L. R., & Siman, R. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-06-03934.1994 · Cited by 316 · see citing works
Self-citation
Simultaneous Degradation of αII- and βII-Spectrin by Caspase 3 (CPP32) in Apoptotic Cells
Wang, K., Posmantur, R. M., Nath, R., McGinnis, K., Whitton, M. M., Talanian, R. V., Glantz, S. B., & Morrow, J. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.35.22490 · Cited by 312 · see citing works
Detection of a Novel Intraneuronal Pool of Insoluble Amyloid β Protein that Accumulates with Time in Culture
Skovronsky, D. M., Doms, R. W., & Lee, V. M.-Y. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.1031 · Cited by 290 · see citing works
Mutations of the presenilin I gene in families with early-onset Alzheimer's disease
Campion, D., Flaman, J., Brice, A., Hannequin, D., Dubois, B., Martin, C., Moreau, V., Charbonnier, F., Didierjean, O., Tardieu, S., et al. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.12.2373 · Cited by 277 · see citing works
Culturing Nerve Cells
(1998) · The MIT Press eBooks · doi:10.7551/mitpress/4913.001.0001 · Cited by 272 · see citing works
Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation
Lopera, F. J. (1997) · JAMA · doi:10.1001/jama.277.10.793 · Cited by 255 · see citing works
Modulation of Secreted β-Amyloid Precursor Protein and Amyloid β-Peptide in Brain by Cholesterol
Howland, D., Trusko, S. P., Savage, M. J., Reaume, A. G., Lang, D. M., Hirsch, J. D., Maeda, N., Siman, R., Greenberg, B., Scott, R. W., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.26.16576 · Cited by 254 · see citing works
Self-citation
Presenilins, the Endoplasmic Reticulum, and Neuronal Apoptosis in Alzheimer's Disease
Mattson, M. P., Guo, Q., Furukawa, K., & Pedersen, W. A. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010001.x · Cited by 246 · see citing works
Evidence That Wallerian Degeneration and Localized Axon Degeneration Induced by Local Neurotrophin Deprivation Do Not Involve Caspases
Finn, J. T., Weil, M., Archer, F., Siman, R., Srinivasan, A. N., & RAFF, M. C. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-04-01333.2000 · Cited by 241 · see citing works
Self-citation
A “knockdown” mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1
McDevitt, M. A., Shivdasani, R. A., Fujiwara, Y., Yang, H., & Orkin, S. H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6781 · Cited by 222 · see citing works
Presenilin mutations associated with Alzheimer disease cause defective intracellular trafficking of β-catenin,a component of the presenilin protein complex
Nishimura, M., Yu, G., Lévesque, G., Zhang, D. M., Ruel, L., Chen, F., Milman, P., Holmes, E., Liang, Y., Kawarai, T., et al. (1999) · Nature Medicine · doi:10.1038/5526 · Cited by 218 · see citing works
Turnover of Amyloid β-Protein in Mouse Brain and Acute Reduction of Its Level by Phorbol Ester
Savage, M. J., Trusko, S. P., Howland, D. S., Pinsker, L. R., Mistretta, S., Reaume, A. G., Greenberg, B. D., Siman, R., & Scott, R. W. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-05-01743.1998 · Cited by 213 · see citing works
Self-citation
G Protein-Mediated Neuronal DNA Fragmentation Induced by Familial Alzheimer's Disease-Associated Mutants of APP
Yamatsuji, T., Matsui, T., Okamoto, T., Komatsuzaki, K., Takeda, S., Fukumoto, H., Iwatsubo, T., Suzuki, N., Asami-Odaka, A., Ireland, S., et al. (1996) · Science · doi:10.1126/science.272.5266.1349 · Cited by 210 · see citing works
Increased Vulnerability of Hippocampal Neurons from Presenilin‐1 Mutant Knock‐In Mice to Amyloid β‐Peptide Tox: Central Roles of Superoxide Production and Caspase Activation
Guo, Q., Sebastian, L., Sopher, B. L., Miller, M. W., Ware, C. B., Martin, G. M., & Mattson, M. P. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721019.x · Cited by 197 · see citing works
Presenilin 1 Facilitates the Constitutive Turnover of β-Catenin: Differential Activity of Alzheimer’s Disease–Linked PS1 Mutants in the β-Catenin–Signaling Pathway
Kang, D. E., Soriano, S., Frosch, M. P., Collins, T., Naruse, S., Sisodia, S. S., Leibowitz, G., Levine, F., & Koo, E. H. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04229.1999 · Cited by 193 · see citing works
Excitotoxic Neurodegeneration in Alzheimer Disease
Olney, J. W. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550220042012 · Cited by 190 · see citing works
Cerebral Amyloid Induces Aberrant Axonal Sprouting and Ectopic Terminal Formation in Amyloid Precursor Protein Transgenic Mice
Phinney, A. L., Deller, T., Stalder, M., Calhoun, M. E., Frotscher, M., Sommer, B., Staufenbiel, M., & Jucker, M. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-19-08552.1999 · Cited by 187 · see citing works
Inhibition of presenilin 1 expression is promoted by p53 and p21WAF-1and results in apoptosis and tumor suppression
Roperch, J.-P., Alvaro, V., Prieur, S., Tuynder, M., Nemani, M., Lethrosne, F., Piouffre, L., Gendron, M., Israeli, D., Dausset, J. B., et al. (1998) · Nature Medicine · doi:10.1038/nm0798-835 · Cited by 175 · see citing works
Light and Electron Microscopic Localization of Presenilin-1 in Primate Brain
Lah, J. J., Heilman, C. J., Nash, N. R., Rees, H. D., Yi, H., Counts, S. E., & Levey, A. I. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-06-01971.1997 · Cited by 168 · see citing works
Neuronal cell death in Alzheimer's disease correlates with apoE uptake and intracellular Abeta stabilization.
LaFerla, F. M., Troncoso, J. C., Strickland, D. K., Kawas, C. H., & Jay, G. D. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119536 · Cited by 162 · see citing works
Enhanced Amyloidogenic Processing of the β-Amyloid Precursor Protein in Gene-targeted Mice Bearing the Swedish Familial Alzheimer's Disease Mutations and a “Humanized” Aβ Sequence
Reaume, A. G., Howland, D. S., Trusko, S. P., Savage, M. J., Lang, D. M., Greenberg, B. D., Siman, R., & Scott, R. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.38.23380 · Cited by 150 · see citing works
Self-citation
Mutant Presenilin-1 Induces Apoptosis and Downregulates Akt/PKB
Weihl, C. C., Ghadge, G. D., Kennedy, S. G., Hay, N., Miller, R. J., & Roos, R. P. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-13-05360.1999 · Cited by 137 · see citing works
Requirement of the Familial Alzheimer's Disease Gene PS2 for Apoptosis
Vito, P., Wolozin, B. L., Ganjei, J. K., Iwasaki, K., Lacaná, E., & D'adamio, L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31025 · Cited by 131 · see citing works
Activation of Neuronal Caspase-3 by Intracellular Accumulation of Wild-Type Alzheimer Amyloid Precursor Protein
Uetsuki, T., Takemoto, K., Nishimura, I., Okamoto, M., Niinobe, M., Momoi, T., Miura, M., & Yoshikawa, K. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-16-06955.1999 · Cited by 129 · see citing works
Enhancement of amyloid β 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease
Murayama, O., Tomita, T., Nihonmatsu, N., Murayama, M., Sun, X., Honda, T., Iwatsubo, T., & Takashima, A. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00187-1 · Cited by 126 · see citing works
Familial Alzheimer's chromosome 14 mutations
Wasco, W., Pettingell, W. P., Jondro, P. D., Schmidt, S. D., Gurubhagavatula, S., Rodes, L., Di-Blasi, T., Romano, D., Guénette, S. Y., Kovacs, D. M., et al. (1995) · Nature Medicine · doi:10.1038/nm0995-848a · Cited by 109 · see citing works
Apoptotic Activities of Wild-Type and Alzheimer's Disease-Related Mutant Presenilins in Drosophila melanogaster
Ye, Y., & Fortini, M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.6.1351 · Cited by 107 · see citing works
Interaction of Alzheimer's Presenilin-1 and Presenilin-2 with Bcl-XL
Passer, B. J., Pellegrini, L., Vito, P., Ganjei, J. K., & D'adamio, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.24007 · Cited by 106 · see citing works
DegenerationIn Vivoof Rat Hippocampal Neurons by Wild-Type Alzheimer Amyloid Precursor Protein Overexpressed by Adenovirus-Mediated Gene Transfer
Nishimura, I., Uetsuki, T., Dani, S. U., Ohsawa, Y., Saito, I., Okamura, H., Uchiyama, Y., & Yoshikawa, K. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-07-02387.1998 · Cited by 103 · see citing works
Overexpression in Neurons of Human Presenilin-1 or a Presenilin-1 Familial Alzheimer Disease Mutant Does Not Enhance Apoptosis
Bursztajn, S., DeSouza, R., McPhie, D. L., Berman, S. A., Shioi, J., Robakis, N. K. R. K., & Neve, R. L. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09790.1998 · Cited by 102 · see citing works
Mutant Presenilin 2 Transgenic Mouse: Effect on an Age‐Dependent Increase of Amyloid β‐Protein 42 in the Brain
Oyama, F., Sawamura, N., Kobayashi, K., Morishima‐Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T. C., Iwatsubo, T., et al. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71010313.x · Cited by 92 · see citing works
Presenilin 1 Suppresses the Function of C-Jun Homodimers via Interaction with Qm/Jif-1
Imafuku, I., Masaki, T., Waragai, M., Takeuchi, S., Kawabata, M., Hirai, S., Ohno, S., Nee, L. E., Lippa, C. F., Kanazawa, I., et al. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.1.121 · Cited by 75 · see citing works
Accumulation of murine amyloidβ42 in a gene‐dosage‐dependent manner in PS1 ‘knock‐in’ mice
Nakano, Y., Kondoh, G., Kudo, T., Imaizumi, K., Kato, M., Miyazaki, J., Tohyama, M., Takeda, J., & Takeda, M. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00698.x · Cited by 72 · see citing works
Calpain Inhibitor I Increases β-Amyloid Peptide Production by Inhibiting the Degradation of the Substrate of γ-Secretase
Zhang, L., Song, L., & Parker, E. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.8966 · Cited by 70 · see citing works
Characterization of human presenilin 1 transgenic rats: increased sensitivity to apoptosis in primary neuronal cultures
Czech, C., Lesort, M. J., Tremp, G. L., Terro, F., Blanchard, V., Schombert, B., Carpentier, N., Dreisler, S., Bonici, B., Takashima, A., et al. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00162-6 · Cited by 49 · see citing works
Rank-Order of Potencies for Inhibition of the Secretion of Aβ40 and Aβ42 Suggests That Both Are Generated by a Single γ-Secretase
Durkin, J. T., Murthy, S., Husten, E. J., Trusko, S. P., Savage, M. J., Rotella, D. P., Greenberg, B., & Siman, R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20499 · Cited by 43 · see citing works
Self-citation
Immunolocalization of caspase proteolysis in situ: evidence for widespread caspase-mediated apoptosis of neurons and glia in the postnatal rat brain
Siman, R., Bozyczko‐Coyne, D., Meyer, S. L., & Bhat, R. V. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00034-2 · Cited by 34 · see citing works
Self-citation
The calcium-activated protease calpain I and ischemia-induced neurodegeneration.
Siman, R., Bozyczko‐Coyne, D., Mj, S., & Roberts‐Lewis, J. M. (1996) · PubMed · Cited by 21 · see citing works
Self-citation
Accumulation of murine amyloid β42 in a gene-dosage-dependent manner in PS1 'knock-in' mice
中野, 有. (2000) · doi:10.11501/3169248 · Cited by 11 · see citing works
New 'Alzheimer's Mouse' Produced
Marx, J. L. (1996) · Science · doi:10.1126/science.274.5285.177 · Cited by 6 · see citing works

Flagged first, then by citations

1 of the 83 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

Siman R, Durkin JT, Husten EJ, Savage MJ, Murthy S, Mistretta S, Chatterjee S, Rotella DP, Dembofsky B, Poorman R, Greenberg BD (1995) Genesis and degradation of A␤ protein by cultured human neu- roblastoma cells. In: Research advances in Alzheimer's disease and related disorders (Iqbal K, Mortimer J, Winblad B, Wisniewski H, eds), pp 675-684. Sussex, UK: Wiley.

Sorted by citations

GSK-3α regulates production of Alzheimer's disease amyloid-β peptides
Phiel, C. J., Wilson, C., Lee, V. M. ‐., & Klein, P. S. (2003) · Nature · doi:10.1038/nature01640 · Cited by 1,200 · 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
Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease
Garcia-Alloza, M., Robbins, E. M., Zhang-Nunes, S. X., Purcell, S. M., Betensky, R. A., Raju, S., Prada, C., Greenberg, S. M., Bacskai, B. J., & Frosch, M. P. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.08.017 · Cited by 744 · see citing works
The presenilin hypothesis of Alzheimer’s disease: Evidence for a loss-of-function pathogenic mechanism.
Shen, J., & Kelleher, R. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608332104 · Cited by 485 · see citing works
Presenilins and -Secretase: Structure, Function, and Role in Alzheimer DiseasePreprint
Strooper, B. D., Iwatsubo, T., & Wolfe, M. S. (2011) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006304 · Cited by 465 · see citing works
A CBP Binding Transcriptional Repressor Produced by the PS1/ϵ-Cleavage of N-Cadherin Is Inhibited by PS1 FAD Mutations
Marambaud, P., Wen, P. H., Dutt, A., Shioi, J., Takashima, A., Siman, R., & Robakis, N. K. R. K. (2003) · Cell · doi:10.1016/j.cell.2003.08.008 · Cited by 465 · see citing works
Self-citation
Practical considerations for choosing a mouse model of Alzheimer’s disease
Jankowsky, J. L., & Zheng, H. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0231-7 · Cited by 449 · see citing works
The two faces of protein misfolding: gain‐ and loss‐of‐function in neurodegenerative diseases
Winklhofer, K. F., Tatzelt, J., & Haass, C. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601930 · Cited by 395 · see citing works
Massive CA1/2 Neuronal Loss with Intraneuronal and N-Terminal Truncated Aβ42 Accumulation in a Novel Alzheimer Transgenic Model
Casas, C., Sergeant, N., Itier, J.-M., Blanchard, V., Wirths, O., van der Kolk, N., Vingtdeux, V., van de Steeg, E., Ret, G., Canton, T., et al. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63388-3 · Cited by 400 · 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
Loss‐of‐function presenilin mutations in Alzheimer disease
Strooper, B. D. (2007) · EMBO Reports · doi:10.1038/sj.embor.7400897 · Cited by 351 · see citing works
Mouse models of Alzheimer's disease
Hall, A. M., & Roberson, E. D. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.11.017 · Cited by 317 · see citing works
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Savage, M. J., Lin, Y.-G., Ciallella, J. R., Flood, D. G., & Scott, R. W. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03376.2002 · Cited by 291 · see citing works
Self-citation
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Zhang, C., McNeil, E. M., Dressler, L., & Siman, R. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.09.018 · Cited by 217 · see citing works
Self-citation
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Li, R., Yang, L., Lindholm, K., Konishi, Y., Yue, X., Hampel, H., Zhang, D., & Shen, Y. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4580-03.2004 · Cited by 177 · see citing works
Caspases, Apoptosis, and Alzheimer Disease: Causation, Correlation, and Confusion
Roth, K. A. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.9.829 · Cited by 175 · see citing works
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Zhang, X., Li, Y., Xu, H., & Zhang, Y. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00427 · Cited by 164 · see citing works
Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration
Koo, E. H., & Kopan, R. (2004) · Nature Medicine · doi:10.1038/nm1065 · Cited by 154 · see citing works
Presenilin function and γ‐secretase activity
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(2008) · Handbook of Clinical Neurology · doi:10.1016/s0072-9752(07)01223-7 · Cited by 137 · see citing works
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Sompol, P. M., Ittarat, W., Tangpong, J., Chen, Y., Doubinskaia, I. E., Batinic-Haberle, I., Abdul, H. M., Butterfield, D. A., & Clair, D. K. S. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.044 · Cited by 134 · see citing works
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Abdul, H. M., Rukhsana Sultana, A., Keller, J. N., Clair, D. K. S., Markesbery, W. R., & Butterfield, D. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03647.x · Cited by 114 · see citing works
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Rao, M. V., Mohan, P. S., Peterhoff, C. M., Yang, D., Schmidt, S., Stavrides, P. H., Campbell, J., Chen, Y., Jiang, Y., Paskevich, P. A., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4119-08.2008 · Cited by 107 · see citing works
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Duggan, S. P., & McCarthy, J. V. (2015) · Cellular Signalling · doi:10.1016/j.cellsig.2015.10.006 · Cited by 100 · see citing works
Cognitive impairment in humanized APP×PS1 mice is linked to Aβ1–42 and NOX activation
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Strooper, B. D. (2007) · Cited by 97 · see citing works
A ketogenic diet improves motor performance but does not affect β-amyloid levels in a mouse model of Alzheimer's Disease
Beckett, T. L., Studzinski, C. M., Keller, J. N., Murphy, M. P., & Niedowicz, D. M. (2013) · Brain Research · doi:10.1016/j.brainres.2013.01.046 · Cited by 94 · see citing works
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Siman, R. G., Flood, D. G., Thinakaran, G., & Neumar, R. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104092200 · Cited by 93 · see citing works
Self-citation
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Wang, R., Tang, P., Wang, P., Boissy, R. E., & Zheng, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509822102 · Cited by 90 · see citing works
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Huang, Q.-Z., Aluise, C., Joshi, G., Sultana, R., Clair, D. S., Markesbery, W., & Butterfield, D. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22422 · Cited by 86 · see citing works
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Murphy, M. P., Beckett, T. L., Ding, Q., Patel, E., Markesbery, W. R., Clair, D. K. S., LeVine, H., & Keller, J. N. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.06.002 · Cited by 85 · see citing works
A Presenilin-1 Mutation Identified in Familial Alzheimer Disease with Cotton Wool Plaques Causes a Nearly Complete Loss of γ-Secretase Activity
Heilig, E. A., Xia, W., Shen, J., & Kelleher, R. J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.116962 · Cited by 87 · see citing works
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Lilliehöök, C., Chan, S. L., Choi, E., Zaidi, N. F., Wasco, W., Mattson, M. P., & Buxbaum, J. D. (2002) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2001.1096 · Cited by 86 · see citing works
Transgenic mouse models of Alzheimer's disease
Hock, B. J., & Lamb, B. T. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02449-0 · Cited by 85 · see citing works
A transgenic rat model of Alzheimer's disease with extracellular Aβ deposition
Flood, D. G., Lin, Y., Lang, D. M., Trusko, S. P., Hirsch, J. D., Savage, M. J., Scott, R. W., & Howland, D. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.10.006 · Cited by 85 · see citing works
Self-citation
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Self-citation
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Presenilin transgenic mice as models of Alzheimer’s disease
Elder, G. A., Sosa, M. A. G., Gasperi, R. D., Dickstein, D. L., & Hof, P. R. (2009) · Brain Structure and Function · doi:10.1007/s00429-009-0227-3 · Cited by 76 · see citing works
Alzheimer's Disease-Linked Mutations in Presenilin-1 Result in a Drastic Loss of Activity in Purified γ-Secretase Complexes
Cacquevel, M., Aeschbach, L., Houacine, J., & Fraering, P. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035133 · Cited by 75 · see citing works
Wild-type Presenilin 1 Protects against Alzheimer Disease Mutation-induced Amyloid Pathology
Wang, R., Wang, B., He, W., & Zheng, H. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512574200 · Cited by 73 · see citing works
Neurons overexpressing mutant presenilin‐1 are more sensitive to apoptosis induced by endoplasmic reticulum‐Golgi stress
Terro, F., Czech, C., Esclaire, F., Elyaman, W., Yardin, C., Baclet, M., Touchet, N., Tremp, G. L., Pradier, L., & Hugon, J. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10312 · Cited by 72 · see citing works
Redox proteomics identification of oxidatively modified proteins in Alzheimer's disease brain and in vivo and in vitro models of AD centered around Aβ(1–42)☆
Rukhsana Sultana, A., Marzia Perluigi, A., & Butterfield, D. A. (2005) · Journal of Chromatography B · doi:10.1016/j.jchromb.2005.09.024 · Cited by 72 · see citing works
Introduction of pathogenic mutations into the mouse Psen1 gene by Base Editor and Target-AID
Sasaguri, H., Nagata, K., Sekiguchi, M., Fujioka, R., Matsuba, Y., Hashimoto, S., Sato, K., Kurup, D., Yokota, T., & Saido, T. C. (2018) · Nature Communications · doi:10.1038/s41467-018-05262-w · Cited by 69 · see citing works
Amyloid-β plaque formation and reactive gliosis are required for induction of cognitive deficits in App knock-in mouse models of Alzheimer’s disease
Sakakibara, Y., Sekiya, M., Saito, T., Saido, T. C., & Iijima, K. M. (2019) · BMC Neuroscience · doi:10.1186/s12868-019-0496-6 · Cited by 65 · see citing works
The functional neurophysiology of the amyloid precursor protein (APP) processing pathway
Randall, A. D., Witton, J., Booth, C., Hynes-Allen, A. M., & Brown, J. T. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.02.011 · Cited by 64 · see citing works
Deletion of Presenilin 1 Hydrophilic Loop Sequence Leads to Impaired γ-Secretase Activity and Exacerbated Amyloid Pathology
Deng, Y., Tarassishin, L., Kallhoff, V., Peethumnongsin, E., Wu, L., Li, Y., & Zheng, H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5384-05.2006 · Cited by 64 · see citing works
Alzheimer’s disease and Alzheimer’s dementia: distinct but overlapping entities
Blass, J. P. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00036-2 · Cited by 62 · see citing works
PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release
Lee, S., Hwang, D. Y., Kim, Y. K., Lee, J. W., Shin, I. C., Oh, K. W., Lee, M. K., Lim, J., Yoon, D. Y., Hwang, S. J., et al. (2006) · The FASEB Journal · doi:10.1096/fj.05-4017fje;1 · Cited by 60 · see citing works
NFATs and Alzheimer's Disease.
Abdul, H. M., Furman, J. L., Sama, M. A., Mathis, D. M., & Norris, C. M. (2010) · PubMed · Cited by 57 · see citing works
Presenilin-1 but not amyloid precursor protein mutations present in mouse models of Alzheimer’s disease attenuate the response of cultured cells to γ-secretase modulators regardless of their potency and structure
Hahn, S., Brüning, T., Neß, J., Czirr, E., Baches, S., Gijsen, H. J. M., Korth, C., Pietrzik, C. U., Bulic, B., & Weggen, S. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07118.x · Cited by 56 · see citing works
Transgenic mice expressing the PS1-A246E mutation: effects on spatial learning, exploration, anxiety, and motor coordination
Lalonde, R., Qian, S., & Strazielle, C. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00230-9 · Cited by 54 · see citing works
Meningoencephalitis associated with passive immunization of a transgenic murine model of Alzheimer's amyloidosis
Lee, E. B., Leng, L. Z., Lee, V. M. ‐., & Trojanowski, J. Q. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.03.070 · Cited by 52 · see citing works
Cortical iron regulation and inflammatory response in Alzheimer's disease and APPSWE/PS1ΔE9 mice: a histological perspective
Meadowcroft, M. D., Connor, J. R., & Yang, Q. X. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00255 · Cited by 51 · see citing works
Time sequence of oxidative stress in the brain from transgenic mouse models of Alzheimer's disease related to the amyloid-β cascade
Belkacemi, A., & Ramassamy, C. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.11.020 · Cited by 49 · see citing works
Formation of Tau Inclusions in Knock-in Mice with Familial Alzheimer Disease (FAD) Mutation of Presenilin 1 (PS1)
Tanemura, K., Chui, D.-H., Fukuda, T., Murayama, M., Park, J.-M., Akagi, T., Tatebayashi, Y., Miyasaka, T., Kimura, T., Hashikawa, T., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509145200 · Cited by 48 · see citing works
Generation of Transgenic Zebrafish Expressing Green Fluorescent Protein Under Control of Zebrafish Amyloid Precursor Protein Gene Regulatory Elements
Lee, J.-A., & Cole, G. J. (2007) · Zebrafish · doi:10.1089/zeb.2007.0516 · Cited by 47 · see citing works
Proteomic analysis of brain proteins in APP/PS‐1 human double mutant knock‐in mice with increasing amyloid β‐peptide deposition: Insights into the effects of in vivo treatment with N‐acetylcysteine as a potential therapeutic intervention in mild cognitive impairment and Alzheimer's disease
Robinson, R. A. S., Gururaj Joshi, A., Huang, Q., Rukhsana Sultana, A., Baker, A. S., Cai, J., Pierce, W. M. J., Clair, D. K. S., Markesbery, W. R., & Butterfield, D. A. (2011) · PROTEOMICS · doi:10.1002/pmic.201000523 · Cited by 46 · see citing works
Transgenic models of Alzheimer's disease: Better utilization of existing models through viral transgenesis
Platt, T. L., Reeves, V. L., & Murphy, M. P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.04.017 · Cited by 46 · see citing works
Integration of Drosophila and Human Genetics to Understand Notch Signaling Related Diseases
Salazar, J. L., & Yamamoto, S. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-89512-3_8 · Cited by 46 · see citing works
Brain transcriptome analysis of a familial Alzheimer’s disease-like mutation in the zebrafish presenilin 1 gene implies effects on energy production
Newman, M., Hin, N., Pederson, S., & Lardelli, M. T. (2019) · Molecular Brain · doi:10.1186/s13041-019-0467-y · Cited by 44 · see citing works
Unbiased screen reveals ubiquilin-1 and -2 highly associated with huntingtin inclusions
Rutherford, N. J., Lewis, J. M., Clippinger, A. K., Thomas, M. A., Adamson, J. L., Cruz, P. E., Cannon, A. D., Xu, G. M., Golde, T. E., Shaw, G., et al. (2013) · Brain Research · doi:10.1016/j.brainres.2013.06.006 · Cited by 44 · see citing works
Genetic Mouse Models of Neurodegenerative Diseases
Trancikova, A. K., Ramonet, D., & Moore, D. J. (2011) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-384878-9.00012-1 · Cited by 46 · see citing works
Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease (Erratum)
Chouliaras, L., Sierksma, A. S. R., Kenis, G., Prickaerts, J., Lemmens, M. A. M., Brasnjevic, I., van Donkelaar, E. L., Martínez‐Martínez, P., Losen, M. H., Baets, M. H. D., et al. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/356862 · Cited by 44 · see citing works
Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2
Hin, N., Newman, M., Kaslin, J., Douek, A. M., Lumsden, A. L., Nik, S. H. M., Dong, Y., Zhou, X., Manucat-Tan, N. B., Ludington, A. J., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227258 · Cited by 40 · see citing works
Age-related loss of phospholipid asymmetry in APP /APP x PS-1 /PS-1 human double mutant knock-in mice: Relevance to Alzheimer disease
Lange, M. L. B., Clair, D. K. S., Markesbery, W. R., Studzinski, C. M., Murphy, M. P., & Butterfield, D. A. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.01.004 · Cited by 41 · see citing works
Proteomic identification of specifically carbonylated brain proteins in APPNLh/APPNLh×PS-1P264L/PS-1P264L human double mutant knock-in mice model of Alzheimer disease as a function of age
Sultana, R., Robinson, R. A. S., Di Domenico, F., Abdul, H. M., Clair, D. K. S., Markesbery, W. R., Cai, J., Pierce, W. M., & Butterfield, D. A. (2011) · Journal of Proteomics · doi:10.1016/j.jprot.2011.06.015 · Cited by 41 · see citing works
Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease
Canales-Aguirre, A. A., Hernández-Sapiéns, M. A., Reza-Zaldívar, E. E., Márquez-Aguirre, A. L., Gómez‐Pinedo, U., Matías‐Guiu, J., Cevallos, R. R., Mateos‐Díaz, J. C., & Sánchez-González, V. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.313016 · Cited by 41 · see citing works
Modeling Alzheimer’s Disease in Mouse without Mutant Protein Overexpression: Cooperative and Independent Effects of Aβ and Tau
Guo, Q., Li, H., Cole, A. L., Hur, J., Li, Y., & Zheng, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080706 · Cited by 38 · see citing works
Molecular Determinants and Thermodynamics of the Amyloid Precursor Protein Transmembrane Domain Implicated in Alzheimer's Disease
Wang, H., Barreyro, L., Provasi, D., Djemil, I., Torres-Arancivia, C., Filizola, M., & Ubarretxena‐Belandia, I. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.03.028 · Cited by 35 · see citing works
Relevance of transgenic mouse models for Alzheimer's disease
Tai, L. M., Weng, J. M., LaDu, M. J., & Brady, S. T. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.07.007 · Cited by 37 · see citing works
NF-κB activated by ER calcium release inhibits Aβ-mediated expression of CHOP protein: Enhancement by AD-linked mutant presenilin 1
Schapansky, J., Olson, K. L., der Ploeg, R. V., & Glazner, G. W. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.04.009 · Cited by 35 · see citing works
Genetic variants associated with neurodegenerative Alzheimer disease in natural models
Salazar, C., Valdivia, G., Ardiles, Á. O., Ewer, J., & Palacios, A. G. (2016) · Biological Research · doi:10.1186/s40659-016-0072-9 · Cited by 33 · see citing works
Gamma-secretase subunit composition and distribution in the presenilin wild-type and mutant mouse brain
Siman, R., & Salidas, S. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.028 · Cited by 33 · see citing works
Self-citation
Gene Therapy Models of Alzheimer’s Disease and Other Dementias
Combs, B., Kneynsberg, A., & Kanaan, N. M. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3271-9_25 · Cited by 31 · see citing works
Pyroglutamate-Modified Amyloid-β Protein Demonstrates Similar Properties in an Alzheimer's Disease Familial Mutant Knock-In Mouse and Alzheimer's Disease Brain
Wu, G., Miller, R. A., Connolly, B., Marcus, J., Renger, J. J., & Savage, M. J. (2013) · Neurodegenerative Diseases · doi:10.1159/000353634 · Cited by 31 · see citing works
Self-citation
Drebrin in Alzheimer’s Disease
Ishizuka, Y., & Hanamura, K. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-4-431-56550-5_12 · Cited by 30 · see citing works
Gene-Environment Interaction Research and Transgenic Mouse Models of Alzheimer's Disease
Chouliaras, L., Sierksma, A. S. R., Kenis, G., Prickaerts, J., Lemmens, M. A. M., Brasnjevic, I., van Donkelaar, E. L., Martínez‐Martínez, P., Losen, M. H., Baets, M. H. D., et al. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/859101 · Cited by 30 · see citing works
Robust cytoplasmic accumulation of phosphorylated TDP-43 in transgenic models of tauopathy
Clippinger, A. K., D’Alton, S., Lin, W.-L., Gendron, T. F., Howard, J. C., Borchelt, D., Cannon, A. D., Carlomagno, Y., Chakrabarty, P., Cook, C. N., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1123-8 · Cited by 29 · see citing works
Deficiency of presenilin‐1 increases calcium‐dependent vulnerability of neurons to oxidative stress in vitro
Nakajima, M., Miura, M., Aosaki, T., & Shirasawa, T. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00478.x · Cited by 28 · see citing works
No post-genetics era in human disease research
Gusella, J. F., & MacDonald, M. E. (2002) · Nature Reviews Genetics · doi:10.1038/nrg706 · Cited by 26 · see citing works
Gastrodia elata Blume and its pure compounds protect BV-2 microglial-derived cell lines against β-amyloid: The involvement of GRP78 and CHOP
Lee, G., Kim, H., Sang-Yong, H., Bhandary, B., Kim, D., Kim, M., So, B., Sun-Young, K., Jo, K.-S., Bo-Hee, L., et al. (2012) · Biological Research · doi:10.4067/s0716-97602012000400013 · Cited by 23 · see citing works
Patient-Derived Fibroblasts With Presenilin-1 Mutations, That Model Aspects of Alzheimer’s Disease Pathology, Constitute a Potential Object for Early Diagnosis
López-Toledo, G., Silva‐Lucero, M., Herrera‐Díaz, J., García, D.-E., Arias‐Montaño, J., & Cárdenas‐Aguayo, M. D. C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.921573 · Cited by 21 · see citing works
Transgenic Mouse Models for the Study of Neurodegenerative Diseases
Marín‐Moreno, A., Canoyra, S., Fernández‐Borges, N., Espinosa, J. C., & Torres, J. M. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2801021 · Cited by 21 · see citing works
Amyloid deposition and advanced age fails to induce Alzheimer's type progression in a double knock-in mouse model.
Malthankar‐Phatak, G. H., Lin, Y., Giovannone, N., & Siman, R. G. (2012) · Europe PMC (PubMed Central) · Cited by 18 · see citing works
Self-citation
Rodent Models of Alzheimer’s Disease: Past Misconceptions and Future Prospects
Collins, H. M., & Greenfield, S. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116222 · Cited by 19 · see citing works
The Presenilin 1 P264L Mutation Presenting as non-Fluent/Agrammatic Primary Progressive Aphasia
Mahoney, C., Downey, L. E., Beck, J. A., Liang, Y., Mead, S., Perry, R. J., & Warren, J. D. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122092 · Cited by 16 · see citing works
Presenilin-1 deficiency impairs glutamate-evoked intracellular calcium responses in neurons
Yang, Y., & Cook, D. G. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2003.11.029 · Cited by 16 · see citing works
A role for presenilin in post‐stress regulation: effects of presenilin mutations on Ca 2+ currents in Drosophila
Lu, Y., Lv, Y., Ye, Y., Wang, Y., Hong, Y., Fortini, M., Zhong, Y., & Xie, Z. (2007) · The FASEB Journal · doi:10.1096/fj.06-6380com · Cited by 15 · see citing works
APPΔNL695 expression in murine tissue downregulates CNBP expression
Niedowicz, D. M., Beckett, T. L., Holler, C. J., Weidner, A. M., & Murphy, M. P. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.07.006 · Cited by 13 · see citing works

Presenilin-1 P264L knock-in mutation: differential effects on A� production, amyloid deposition, and neuronal vulnerability
Siman, R., Reaume, A. G., Savage, M. J., Trusko, S. P., Lin, Y.-G., Scott, R. W., & Flood, D. G. (2000)
Self-citation
Accumulation of murine amyloidβ42 in a gene‐dosage‐dependent manner in PS1 ‘knock‐in’ mice
Nakano, Y., Kondoh, G., Kudo, T., Imaizumi, K., Kato, M., Miyazaki, J., Tohyama, M., Takeda, J., & Takeda, M. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00698.x · Cited by 72 · see citing works
FAD mutant PS-1 gene-targeted mice: increased Aβ42 and Aβ deposition without APP overproduction
Flood, D. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00330-x · Cited by 131 · see citing works
Self-citation
Cortical neurodegeneration caused by Psen1 mutations is independent of Aβ
Yan, K., Zhang, C., Kang, J., Montenegro, P., & Shen, J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2409343121 · Cited by 11 · see citing works
Presenilin P264L knock-in mutation: Differential effects on abproduction, amyloid deposition, and neuronal vulnerability
Siman, R., Reaume, A. G., Savage, M. J., Scott, R. W., & Flood, D. G. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)82329-5 · Cited by 2 · see citing works
Self-citation

Authors: Siman, R., Reaume, A. G., Savage, M. J., Trusko, S., Lin, Y.-G., Scott, R. W., & Flood, D. G.
Affiliations: University of Pennsylvania (US)
ORCID: Reaume, Andrew G.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2000-12-01
Volume: 20
Issue: 23
Pages: 8717-8726
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.20-23-08717.2000
PMC: PMC6773081
OpenAlex: W1651448739
Cited by: 133
References: 83
Citations by year: 2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 10 · 2012: 4
FWCI: 3.06
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
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: presenilin 1, familial Alzheimer's disease, amyloid-beta production, amyloid-beta 42, amyloid deposition, neuronal vulnerability, cortical neurons, apoptosis, staurosporine, caspase activation, calpain, APP processing, reactive gliosis
MeSH terms: Alzheimer Disease, Amyloid, Animals, Calpain, Cell Survival, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Homozygote, Membrane Proteins, Mice, Mutant Strains, Mice, Transgenic, Neurons, Peptide Fragments, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Apoptosis, Gene Targeting, Glutamic Acid, Staurosporine, Amino Acid Substitution, Caspases, Mice, Presenilin-1

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Presenilin-1 P264L Knock-In Mutation: Differential Effects on Aβ Production, Amyloid Deposition, and Neuronal Vulnerability

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