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Are Tangles as Toxic as They Look?
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“This explanation is consistent with previous publications81,82.”
From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [81]
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Citations
Cites
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
Self-citationProfound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796 · cited 2×
“…mature, silver-positive NFT has been thought to contribute to neuronal loss in AD based on the close correlations between NFT pathology, both in terms of location and number, and degree of AD severity and cognitive decline (Arriagada et al. 1992; Giannakopoulos et al. 2003; Gomez-Isla et al. 1996).”
Self-citationNeuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489
Self-citationImpaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease
Wang, X., Su, B., Lee, H.-G., Li, X., Perry, G., Smith, M. A., & Zhu, X. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1357-09.2009 · Cited by 1,224
Differential Regulation of Dynein and Kinesin Motor Proteins by Tau
Dixit, R., Ross, J. L., Goldman, Y. E., & Holzbaur, E. L. F. (2008) · Science · doi:10.1126/science.1152993 · Cited by 1,012
Zempel, H., Thies, E., Mandelkow, E., & Mandelkow, E.-M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.2357-10.2010 · Cited by 686 · cited 1×
“In a more recent study, Zempel et al. (2010) extended this finding to show that oligomeric amyloid beta induced loss of dendritic spines and mitochondrial distribution correlate with mislocalization of tau to dendrites in cultured neurons.”
Caspase activation precedes and leads to tangles
de Calignon, A., Fox, L. M., Pitstick, R., Carlson, G. A., Bacskai, B. J., Spires-Jones, T. L., & Hyman, B. T. (2010) · Nature · doi:10.1038/nature08890 · Cited by 517
Self-citationCell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms
Andorfer, C., Acker, C. M., Kress, Y., Hof, P. R., Duff, K., & Davies, P. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4637-04.2005 · Cited by 511 · cited 3×
“In fact, markers of cell death were not found in NFT bearing neurons in htau mice (Andorfer et al. 2005), indicating that cell death occurs independently of NFT.”
Diagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00062-6 · Cited by 410
Research works printed but not linked: 49
- Allen B, Ingram E, Takao M, Smith MJ, Jakes R, Virdee K, Yoshida H, Holzer M, Craxton M, Emson PC, Atzori C, Migheli A, Crowther RA, Ghetti B, Spillantini MG, Goedert M (2002) Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J Neurosci 22:9340–9351 · DOI
- Alonso Adel C, Li B, Grundke-Iqbal I, Iqbal K (2006) Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity. Proc Natl Acad Sci USA 103:8864–8869 · DOI · Paper page
- Alonso AC, Zaidi T, Grundke-Iqbal I, Iqbal K (1994) Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc Natl Acad Sci USA 91:5562–5566 · DOI · Paper page
- Alonso AC, Grundke-Iqbal I, Iqbal K (1996) Alzheimer's disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 2:783–787 · DOI · Paper page
- Alzheimer A (1907) Ubereine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatr Psych-Gericht Med 64:146–148
- Baas PW, Qiang L (2005) Neuronal microtubules: when the MAP is the roadblock. Trends Cell Biol 15:183–187 · DOI
- Berger Z, Roder H, Hanna A, Carlson A, Rangachari V, Yue M, Wszolek Z, Ashe K, Knight J, Dickson D, Andorfer C, Rosenberry TL, Lewis J, Hutton M, Janus C (2007) Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci 27:3650–3662 · DOI
- Bramblett GT, Goedert M, Jakes R, Merrick SE, Trojanowski JQ, Lee VM (1993) Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding. Neuron 10:1089–1099 · DOI · Paper page
- Bretteville A, Planel E (2008) Tau aggregates: toxic, inert, or protective species? J Alzheimers Dis 14:431–436 · DOI
- Bulic B, Pickhardt M, Khlistunova I, Biernat J, Mandelkow EM, Mandelkow E, Waldmann H (2007) Rhodanine-based tau aggregation inhibitors in cell models of tauopathy. Angew Chem Int Ed Engl 46:9215–9219 · DOI
- Callahan LM, Vaules WA, Coleman PD (1999) Quantitative decrease in synaptophysin message expression and increase in cathepsin D message expression in Alzheimer disease neurons containing neurofibrillary tangles. J Neuropathol Exp Neurol 58:275–287 · DOI
- Chung CW, Song YH, Kim IK, Yoon WJ, Ryu BR, Jo DG, Woo HN, Kwon YK, Kim HH, Gwag BJ, Mook-Jung IH, Jung YK (2001) Proapoptotic effects of tau cleavage product generated by caspase-3. Neurobiol Dis 8:162–172 · DOI
- Congdon EE, Duff KE (2008) Is tau aggregation toxic or protective? J Alzheimers Dis 14:453–457 · DOI
- Darios F, Muriel MP, Khondiker ME, Brice A, Ruberg M (2005) Neurotoxic calcium transfer from endoplasmic reticulum to mitochondria is regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau. J Neurosci 25:4159–4168 · DOI
- Ebneth A, Godemann R, Stamer K, Illenberger S, Trinczek B, Mandelkow E (1998) Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease. J Cell Biol 143:777–794 · DOI · Paper page
- Giannakopoulos P, Herrmann FR, Bussiere T, Bouras C, Kovari E, Perl DP, Morrison JH, Gold G, Hof PR (2003) Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer's disease. Neurology 60:1495–1500 · DOI · Paper page
- Ginsberg SD, Hemby SE, Lee VM, Eberwine JH, Trojanowski JQ (2000) Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann Neurol 48:77–87 · DOI
- Goedert M, Spillantini MG (2006) A century of Alzheimer's disease. Science 314:777–781 · DOI
- Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A (1988) Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 85:4051–4055 · DOI · Paper page
- Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118:5411–5419 · DOI · Paper page
- Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK, Pitstick R, Carlson GA, Lanier LM, Yuan L-L, Ashe KH, Liao D (2010) Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68:1067–1081 · DOI · Paper page
- Hutton M (2001) Missense and splice site mutations in tau associated with FTDP-17: multiple pathogenic mechanisms. Neurology 56:21S–25S · DOI
- Hutton M, Lewis J, Dickson D, Yen SH, McGowan E (2001) Analysis of tauopathies with transgenic mice. Trends Mol Med 7:467–470 · DOI · Paper page
- Iqbal K, Alonso Adel C, Grundke-Iqbal I (2008) Cytosolic abnormally hyperphosphorylated tau but not paired helical filaments sequester normal MAPs and inhibit microtubule assembly. J Alzheimers Dis 14:365–370 · DOI
- Katsuse O, Lin WL, Lewis J, Hutton ML, Dickson DW (2006) Neurofibrillary tangle-related synaptic alterations of spinal motor neurons of P301L tau transgenic mice. Neurosci Lett 409:95–99 · DOI
- Khlistunova I, Biernat J, Wang Y, Pickhardt M, von Bergen M, Gazova Z, Mandelkow E, Mandelkow EM (2006) Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugs. J Biol Chem 281:1205–1214 · DOI
- Kuret J, Congdon EE, Li G, Yin H, Yu X, Zhong Q (2005) Evaluating triggers and enhancers of tau fibrillization. Microsc Res Technol 67:141–155 · DOI
- Lasagna-Reeves CA, Castillo-Carranza DL, Guerrero-Muoz MJ, Jackson GR, Kayed R (2010) Preparation and characterization of neurotoxic tau oligomers. Biochemistry 49:10039–10041 · DOI · Paper page
- Ludvigson AE, Luebke JI, Lewis J, Peters A (2010) Structural abnormalities in the cortex of the rTg4510 mouse model of tauopathy: a light and electron microscopy study. Brain Struct Funct 216:31–42 · DOI
- Mandelkow EM, Stamer K, Vogel R, Thies E, Mandelkow E (2003) Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses. Neurobiol Aging 24:1079–1085 · DOI
- Mocanu M-M, Nissen A, Eckermann K, Khlistunova I, Biernat J, Drexler D, Petrova O, Schonig K, Bujard H, Mandelkow E, Zhou L, Rune G, Mandelkow E-M (2008a) The potential for —structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous tau in inducible mouse models of tauopathy. J Neurosci 28:737–748 · DOI · Paper page
- Mocanu MM, Nissen A, Eckermann K, Khlistunova I, Biernat J, Drexler D, Petrova O, Schonig K, Bujard H, Mandelkow E, Zhou L, Rune G, Mandelkow EM (2008b) The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous Tau in inducible mouse models of tauopathy. J Neurosci 28:737–748 · DOI · Paper page
- Reed LA, Wszolek ZK, Hutton M (2001) Phenotypic correlations in FTDP-17. Neurobiol Aging 22:89–107 · DOI
- Rocher AB, Crimins JL, Amatrudo JM, Kinson MS, Todd-Brown MA, Lewis J, Luebke JI (2010) Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Exp Neurol 223:385–393 · DOI · Paper page
- SantaCruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309:476–481 · DOI · Paper page
- Selkoe DJ (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81:741–766 · DOI · Paper page
- Spires TL, Hyman BT (2005) Transgenic models of Alzheimer's disease: learning from animals. NeuroRx 2:423–437 · DOI
- Spires-Jones TL, de Calignon A, Matsui T, Zehr C, Pitstick R, Wu HY, Osetek JD, Jones PB, Bacskai BJ, Feany MB, Carlson GA, Ashe KH, Lewis J, Hyman BT (2008) In vivo imaging reveals dissociation between caspase activation and acute neuronal death in tangle-bearing neurons. J Neurosci 28:862–867 · DOI · Paper page
- Spires-Jones TL, Stoothoff WH, de Calignon A, Jones PB, Hyman BT (2009) Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci 32:150–159 · DOI
- Stamer K, Vogel R, Thies E, Mandelkow E, Mandelkow EM (2002) Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J Cell Biol 156:1051–1063 · DOI · Paper page
- Stoothoff WH, Johnson GV (2005) Tau phosphorylation: physiological and pathological consequences. Biochim Biophys Acta 1739:280–297 · DOI
- Stoothoff W, Jones PB, Spires-Jones TL, Joyner D, Chhabra E, Bercury K, Fan Z, Xie H, Bacskai B, Edd J, Irimia D, Hyman BT (2009) Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport. J Neurochem 111:417–427 · DOI · Paper page
- Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G, Mandelkow E, D'Hooge R, Alzheimer C, Mandelkow EM (2010) Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 31:2511–2525 · DOI · Paper page
- Terry RD (2000) Do neuronal inclusions kill the cell? J Neural Transm Suppl 59:91–93
- van de Nes JA, Nafe R, Schlote W (2008) Non-tau based neuronal degeneration in Alzheimer's disease — an immunocytochemical and quantitative study in the supragranular layers of the middle temporal neocortex. Brain Res 1213:152–165 · DOI
- Velasco A, Fraser G, Delobel P, Ghetti B, Lavenir I, Goedert M (2008) Detection of filamentous tau inclusions by the fluorescent Congo red derivative FSB [(trans, trans)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene]. FEBS Lett 582:901–906 · DOI
- Wang YP, Biernat J, Pickhardt M, Mandelkow E, Mandelkow EM (2007) Stepwise proteolysis liberates tau fragments that nucleate the Alzheimer-like aggregation of full-length tau in a neuronal cell model. Proc Natl Acad Sci USA 104:10252–10257 · DOI
- Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, Hutton M, Feany MB (2001) Tauopathy in drosophila: neurodegeneration without neurofibrillary tangles. Science 293:711–714 · DOI · Paper page
- Zehr C, Lewis J, McGowan E, Crook J, Lin WL, Godwin K, Knight J, Dickson DW, Hutton M (2004) Apoptosis in oligodendrocytes is associated with axonal degeneration in P301L tau mice. Neurobiol Dis 15:553–562 · DOI
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“…metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b; Spires-Jones et al., 2011; Cowan et al., 2012).”
BackgroundSoluble forms of tau are toxic in Alzheimer's disease
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GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau
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Metadata
- Authors
- Spires-Jones, T. L., Kopeikina, K. J., Koffie, R. M., de Calignon, A., & Hyman, B. T.
- Venue
- Journal of Molecular Neuroscience
- Published
- 2011-06-03
- Volume
- 45
- Issue
- 3
- Pages
- 438-444
- ISSN
- 0895-8696
- 1559-1166
- PMC
- PMC3173560
- Cited by
- 104
- References
- 16
- Language
- en
- Update notices
- correction (2011-06-28)
- Licence
- www.springer.com/tdm (tdm)
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