Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2011

Open Access 01-12-2011 | Research article

Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice

Authors: Cristian A Lasagna-Reeves, Diana L Castillo-Carranza, Urmi Sengupta, Audra L Clos, George R Jackson, Rakez Kayed

Published in: Molecular Neurodegeneration | Issue 1/2011

Login to get access

Abstract

Background

The correlation between neurofibrillary tangles of tau and disease progression in the brains of Alzheimer's disease (AD) patients remains an area of contention. Innovative data are emerging from biochemical, cell-based and transgenic mouse studies that suggest that tau oligomers, a pre-filament form of tau, may be the most toxic and pathologically significant tau aggregate.

Results

Here we report that oligomers of recombinant full-length human tau protein are neurotoxic in vivo after subcortical stereotaxic injection into mice. Tau oligomers impaired memory consolidation, whereas tau fibrils and monomers did not. Additionally, tau oligomers induced synaptic dysfunction by reducing the levels of synaptic vesicle-associated proteins synaptophysin and septin-11. Tau oligomers produced mitochondrial dysfunction by decreasing the levels of NADH-ubiquinone oxidoreductase (electron transport chain complex I), and activated caspase-9, which is related to the apoptotic mitochondrial pathway.

Conclusions

This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers.
Appendix
Available only for authorised users
Literature
1.
Binder LI, Frankfurter A, Rebhun LI: The distribution of tau in the mammalian central nervous system. J Cell Biol. 1985, 101: 1371-1378. 10.1083/jcb.101.4.1371.PubMedCrossRef
2.
Drechsel DN, Hyman AA, Cobb MH, Kirschner MW: Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell. 1992, 3: 1141-1154.PubMedPubMedCentralCrossRef
3.
Lee VM, Goedert M, Trojanowski JQ: Neurodegenerative tauopathies. Annu Rev Neurosci. 2001, 24: 1121-1159. 10.1146/annurev.neuro.24.1.1121.PubMedCrossRef
4.
Alonso AC, Li B, Grundke-Iqbal I, Iqbal K: Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies. Curr Alzheimer Res. 2008, 5: 375-384. 10.2174/156720508785132307.PubMedCrossRef
5.
Iqbal K, Liu F, Gong CX, Alonso AD, Grundke-Iqbal I: Mechanisms of tau-induced neurodegeneration. Acta Neuropathol. 2009, 118: 53-69. 10.1007/s00401-009-0486-3.PubMedPubMedCentralCrossRef
6.
Ballatore C, Lee VM, Trojanowski JQ: Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci. 2007, 8: 663-672.PubMedCrossRef
7.
Haroutunian V, Davies P, Vianna C, Buxbaum JD, Purohit DP: Tau protein abnormalities associated with the progression of alzheimer disease type dementia. Neurobiol Aging. 2007, 28: 1-7. 10.1016/j.neurobiolaging.2005.11.001.PubMedCrossRef
8.
Braak H, Braak E: Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991, 82: 239-259. 10.1007/BF00308809.PubMedCrossRef
9.
Delacourte A, Buee L: Tau pathology: a marker of neurodegenerative disorders. Curr Opin Neurol. 2000, 13: 371-376. 10.1097/00019052-200008000-00002.PubMedCrossRef
10.
Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K: Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006, 112: 389-404. 10.1007/s00401-006-0127-z.PubMedPubMedCentralCrossRef
11.
Brunden KR, Trojanowski JQ, Lee VM: Evidence that non-fibrillar tau causes pathology linked to neurodegeneration and behavioral impairments. J Alzheimers Dis. 2008, 14: 393-399.PubMedPubMedCentral
12.
Marx J: Alzheimer's disease. A new take on tau. Science. 2007, 316: 1416-1417. 10.1126/science.316.5830.1416.PubMedCrossRef
13.
Andorfer C, Acker CM, Kress Y, Hof PR, Duff K, Davies P: Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci. 2005, 25: 5446-5454. 10.1523/JNEUROSCI.4637-04.2005.PubMedCrossRef
14.
Polydoro M, Acker CM, Duff K, Castillo PE, Davies P: Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J Neurosci. 2009, 29: 10741-10749. 10.1523/JNEUROSCI.1065-09.2009.PubMedPubMedCentralCrossRef
15.
Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM: Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007, 53: 337-351. 10.1016/j.neuron.2007.01.010.PubMedCrossRef
16.
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: Accumulation of pathological tau species and memory loss in a conditional model of tauopathy. J Neurosci. 2007, 27: 3650-3662. 10.1523/JNEUROSCI.0587-07.2007.PubMedCrossRef
17.
Spires TL, Orne JD, SantaCruz K, Pitstick R, Carlson GA, Ashe KH, Hyman BT: Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am J Pathol. 2006, 168: 1598-1607. 10.2353/ajpath.2006.050840.PubMedPubMedCentralCrossRef
18.
Gomez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, Parisi JE, Hyman BT: Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann Neurol. 1997, 41: 17-24. 10.1002/ana.410410106.PubMedCrossRef
19.
Terry RD: Do neuronal inclusions kill the cell?. J Neural Transm Suppl. 2000, 59: 91-93.PubMed
20.
Maeda S, Sahara N, Saito Y, Murayama M, Yoshiike Y, Kim H, Miyasaka T, Murayama S, Ikai A, Takashima A: Granular tau oligomers as intermediates of tau filaments. Biochemistry. 2007, 46: 3856-3861. 10.1021/bi061359o.PubMedCrossRef
21.
Maeda S, Sahara N, Saito Y, Murayama S, Ikai A, Takashima A: Increased levels of granular tau oligomers: an early sign of brain aging and Alzheimer's disease. Neurosci Res. 2006, 54: 197-201. 10.1016/j.neures.2005.11.009.PubMedCrossRef
22.
Yamazaki M, Hasegawa M, Mori O, Murayama S, Tsuchiya K, Ikeda K, Chen KM, Katayama Y, Oyanagi K: Tau-positive fine granules in the cerebral white matter: a novel finding among the tauopathies exclusive to parkinsonism-dementia complex of Guam. J Neuropathol Exp Neurol. 2005, 64: 839-846. 10.1097/01.jnen.0000182977.79483.89.PubMedCrossRef
23.
Neumann K, Farias G, Slachevsky A, Perez P, Maccioni RB: Human Platelets Tau: A Potential Peripheral Marker for Alzheimer's Disease. J Alzheimers Dis.
24.
Congdon EE, Kim S, Bonchak J, Songrug T, Matzavinos A, Kuret J: Nucleation-dependent tau filament formation: the importance of dimerization and an estimation of elementary rate constants. J Biol Chem. 2008, 283: 13806-13816. 10.1074/jbc.M800247200.PubMedPubMedCentralCrossRef
25.
Xu S, Brunden KR, Trojanowski JQ, Lee VM: Characterization of tau fibrillization in vitro. Alzheimers Dement. 2010, 6: 110-117. 10.1016/j.jalz.2009.06.002.PubMedPubMedCentralCrossRef
26.
Huang SM, Mouri A, Kokubo H, Nakajima R, Suemoto T, Higuchi M, Staufenbiel M, Noda Y, Yamaguchi H, Nabeshima T, Saido TC, Iwata N: Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function. J Biol Chem. 2006, 281: 17941-17951. 10.1074/jbc.M601372200.PubMedCrossRef
27.
Mouri A, Noda Y, Hara H, Mizoguchi H, Tabira T, Nabeshima T: Oral vaccination with a viral vector containing Abeta cDNA attenuates age-related Abeta accumulation and memory deficits without causing inflammation in a mouse Alzheimer model. FASEB J. 2007, 21: 2135-2148. 10.1096/fj.06-7685com.PubMedCrossRef
28.
Scholtzova H, Wadghiri YZ, Douadi M, Sigurdsson EM, Li YS, Quartermain D, Banerjee P, Wisniewski T: Memantine leads to behavioral improvement and amyloid reduction in Alzheimer's-disease-model transgenic mice shown as by micromagnetic resonance imaging. J Neurosci Res. 2008, 86: 2784-2791. 10.1002/jnr.21713.PubMedPubMedCentralCrossRef
29.
Zhang L, Xing Y, Ye CF, Ai HX, Wei HF, Li L: Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease and intervention by using tetrahydroxystilbene glucoside. Behav Brain Res. 2006, 173: 246-254. 10.1016/j.bbr.2006.06.034.PubMedCrossRef
30.
Margittai M, Langen R: Template-assisted filament growth by parallel stacking of tau. Proc Natl Acad Sci USA. 2004, 101: 10278-10283. 10.1073/pnas.0401911101.PubMedPubMedCentralCrossRef
31.
Perez M, Valpuesta JM, Medina M, Montejo de Garcini E, Avila J: Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau-tau interaction. J Neurochem. 1996, 67: 1183-1190.PubMedCrossRef
32.
Ball MJ: Neurofibrillary tangles in the dementia of "normal pressure" hydrocephalus. Can J Neurol Sci. 1976, 3: 227-235.PubMed
33.
Bondareff W, Mountjoy CQ, Roth M, Hauser DL: Neurofibrillary degeneration and neuronal loss in Alzheimer's disease. Neurobiol Aging. 1989, 10: 709-715. 10.1016/0197-4580(89)90007-9.PubMedCrossRef
34.
West MJ, Coleman PD, Flood DG, Troncoso JC: Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet. 1994, 344: 769-772. 10.1016/S0140-6736(94)92338-8.PubMedCrossRef
35.
West MJ, Kawas CH, Martin LJ, Troncoso JC: The CA1 region of the human hippocampus is a hot spot in Alzheimer's disease. Ann N Y Acad Sci. 2000, 908: 255-259.PubMedCrossRef
36.
Lasagna-Reeves CA, Castillo-Carranza DL, Guerrero-Muoz MJ, Jackson GR, Kayed R: Preparation and characterization of neurotoxic tau oligomers. Biochemistry. 2010, 49: 10039-10041. 10.1021/bi1016233.PubMedCrossRef
37.
Greene JD, Baddeley AD, Hodges JR: Analysis of the episodic memory deficit in early Alzheimer's disease: evidence from the doors and people test. Neuropsychologia. 1996, 34: 537-551. 10.1016/0028-3932(95)00151-4.PubMedCrossRef
38.
Schmued LC, Hopkins KJ: Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res. 2000, 874: 123-130. 10.1016/S0006-8993(00)02513-0.PubMedCrossRef
39.
Schmued LC, Hopkins KJ: Fluoro-Jade: novel fluorochromes for detecting toxicant-induced neuronal degeneration. Toxicol Pathol. 2000, 28: 91-99. 10.1177/019262330002800111.PubMedCrossRef
40.
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R: Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991, 30: 572-580. 10.1002/ana.410300410.PubMedCrossRef
41.
Coleman PD, Yao PJ: Synaptic slaughter in Alzheimer's disease. Neurobiol Aging. 2003, 24: 1023-1027. 10.1016/j.neurobiolaging.2003.09.001.PubMedCrossRef
42.
Gitler D, Takagishi Y, Feng J, Ren Y, Rodriguiz RM, Wetsel WC, Greengard P, Augustine GJ: Different presynaptic roles of synapsins at excitatory and inhibitory synapses. J Neurosci. 2004, 24: 11368-11380. 10.1523/JNEUROSCI.3795-04.2004.PubMedCrossRef
43.
Mutisya EM, Bowling AC, Beal MF: Cortical cytochrome oxidase activity is reduced in Alzheimer's disease. J Neurochem. 1994, 63: 2179-2184.PubMedCrossRef
44.
Schagger H, Ohm TG: Human diseases with defects in oxidative phosphorylation. 2. F1F0 ATP-synthase defects in Alzheimer disease revealed by blue native polyacrylamide gel electrophoresis. Eur J Biochem. 1995, 227: 916-921. 10.1111/j.1432-1033.1995.tb20219.x.PubMedCrossRef
45.
Kim SH, Vlkolinsky R, Cairns N, Fountoulakis M, Lubec G: The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease. Life Sci. 2001, 68: 2741-2750. 10.1016/S0024-3205(01)01074-8.PubMedCrossRef
46.
David DC, Hauptmann S, Scherping I, Schuessel K, Keil U, Rizzu P, Ravid R, Drose S, Brandt U, Muller WE, Eckert A, Götz J: Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. J Biol Chem. 2005, 280: 23802-23814. 10.1074/jbc.M500356200.PubMedCrossRef
47.
Quintanilla RA, Matthews-Roberson TA, Dolan PJ, Johnson GV: Caspase-cleaved tau expression induces mitochondrial dysfunction in immortalized cortical neurons: implications for the pathogenesis of Alzheimer disease. J Biol Chem. 2009, 284: 18754-18766. 10.1074/jbc.M808908200.PubMedPubMedCentralCrossRef
48.
Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D: Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res. 1987, 436: 30-38. 10.1016/0006-8993(87)91553-8.PubMedCrossRef
49.
Aksenov MY, Tucker HM, Nair P, Aksenova MV, Butterfield DA, Estus S, Markesbery WR: The expression of several mitochondrial and nuclear genes encoding the subunits of electron transport chain enzyme complexes, cytochrome c oxidase, and NADH dehydrogenase, in different brain regions in Alzheimer's disease. Neurochem Res. 1999, 24: 767-774. 10.1023/A:1020783614031.PubMedCrossRef
50.
Mercken M, Vandermeeren M, Lubke U, Six J, Boons J, Vanmechelen E, Van de Voorde A, Gheuens J: Affinity purification of human tau proteins and the construction of a sensitive sandwich enzyme-linked immunosorbent assay for human tau detection. J Neurochem. 1992, 58: 548-553. 10.1111/j.1471-4159.1992.tb09754.x.PubMedCrossRef
51.
Li Q, Lau A, Morris TJ, Guo L, Fordyce CB, Stanley EF: A syntaxin 1, Galpha(o), and N-type calcium channel complex at a presynaptic nerve terminal: analysis by quantitative immunocolocalization. J Neurosci. 2004, 24: 4070-4081. 10.1523/JNEUROSCI.0346-04.2004.PubMedCrossRef
52.
Ashkenazi A, Dixit VM: Apoptosis control by death and decoy receptors. Curr Opin Cell Biol. 1999, 11: 255-260. 10.1016/S0955-0674(99)80034-9.PubMedCrossRef
53.
Rohn TT, Rissman RA, Davis MC, Kim YE, Cotman CW, Head E: Caspase-9 activation and caspase cleavage of tau in the Alzheimer's disease brain. Neurobiol Dis. 2002, 11: 341-354. 10.1006/nbdi.2002.0549.PubMedCrossRef
54.
Haass C, Selkoe DJ: Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol. 2007, 8: 101-112. 10.1038/nrm2101.PubMedCrossRef
55.
Glabe CG: Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging. 2006, 27: 570-575. 10.1016/j.neurobiolaging.2005.04.017.PubMedCrossRef
56.
Caughey B, Baron GS, Chesebro B, Jeffrey M: Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. Annu Rev Biochem. 2009, 78: 177-204. 10.1146/annurev.biochem.78.082907.145410.PubMedPubMedCentralCrossRef
57.
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: Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005, 309: 476-481. 10.1126/science.1113694.PubMedPubMedCentralCrossRef
58.
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: 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. 2008, 28: 737-748. 10.1523/JNEUROSCI.2824-07.2008.PubMedCrossRef
59.
Kayed R, Jackson GR: Prefilament tau species as potential targets for immunotherapy for Alzheimer disease and related disorders. Curr Opin Immunol. 2009, 21: 359-363. 10.1016/j.coi.2009.05.001.PubMedCrossRef
60.
Reed JM, Squire LR: Impaired recognition memory in patients with lesions limited to the hippocampal formation. Behav Neurosci. 1997, 111: 667-675.PubMedCrossRef
61.
Zola SM, Squire LR, Teng E, Stefanacci L, Buffalo EA, Clark RE: Impaired recognition memory in monkeys after damage limited to the hippocampal region. J Neurosci. 2000, 20: 451-463.PubMed
62.
Kril JJ, Patel S, Harding AJ, Halliday GM: Neuron loss from the hippocampus of Alzheimer's disease exceeds extracellular neurofibrillary tangle formation. Acta Neuropathol. 2002, 103: 370-376. 10.1007/s00401-001-0477-5.PubMedCrossRef
63.
Braak H, Braak E: Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol. 1991, 1: 213-216. 10.1111/j.1750-3639.1991.tb00661.x.PubMedCrossRef
64.
Delacourte A, Sergeant N, Wattez A, Maurage CA, Lebert F, Pasquier F, David JP: Tau aggregation in the hippocampal formation: an ageing or a pathological process?. Exp Gerontol. 2002, 37: 1291-1296. 10.1016/S0531-5565(02)00141-9.PubMedCrossRef
65.
Brundin P, Melki R, Kopito R: Prion-like transmission of protein aggregates in neurodegenerative diseases. Nat Rev Mol Cell Biol. 2010, 11: 301-307. 10.1038/nrm2873.PubMedPubMedCentralCrossRef
66.
Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A, Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M: Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol. 2009, 11: 909-913. 10.1038/ncb1901.PubMedPubMedCentralCrossRef
67.
68.
Gomez-Ramos A, Diaz-Hernandez M, Cuadros R, Hernandez F, Avila J: Extracellular tau is toxic to neuronal cells. FEBS Lett. 2006, 580: 4842-4850. 10.1016/j.febslet.2006.07.078.PubMedCrossRef
69.
Frost B, Jacks RL, Diamond MI: Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem. 2009, 284: 12845-12852. 10.1074/jbc.M808759200.PubMedPubMedCentralCrossRef
70.
Diaz-Hernandez M, Gomez-Ramos A, Rubio A, Gomez-Villafuertes R, Naranjo JR, Miras-Portugal MT, Avila J: Tissue-nonspecific alkaline phosphatase promotes the neurotoxicity effect of extracellular tau. J Biol Chem. 2010, 285: 32539-32548. 10.1074/jbc.M110.145003.PubMedPubMedCentralCrossRef
71.
Davey GP, Peuchen S, Clark JB: Energy thresholds in brain mitochondria. Potential involvement in neurodegeneration. J Biol Chem. 1998, 273: 12753-12757. 10.1074/jbc.273.21.12753.PubMedCrossRef
72.
Davey GP, Clark JB: Threshold effects and control of oxidative phosphorylation in nonsynaptic rat brain mitochondria. J Neurochem. 1996, 66: 1617-1624.PubMedCrossRef
73.
Bigio EH, Vono MB, Satumtira S, Adamson J, Sontag E, Hynan LS, White CL, Baker M, Hutton M: Cortical synapse loss in progressive supranuclear palsy. J Neuropathol Exp Neurol. 2001, 60: 403-410.PubMedCrossRef
74.
Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC: Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol. 2001, 58: 1395-1402. 10.1001/archneur.58.9.1395.PubMedCrossRef
75.
Suzuki M, Desmond TJ, Albin RL, Frey KA: Cholinergic vesicular transporters in progressive supranuclear palsy. Neurology. 2002, 58: 1013-1018.PubMedCrossRef
76.
Thies E, Mandelkow EM: Missorting of tau in neurons causes degeneration of synapses that can be rescued by the kinase MARK2/Par-1. J Neurosci. 2007, 27: 2896-2907. 10.1523/JNEUROSCI.4674-06.2007.PubMedCrossRef
77.
Kimura T, Fukuda T, Sahara N, Yamashita S, Murayama M, Mizoroki T, Yoshiike Y, Lee B, Sotiropoulos I, Maeda S, Takashima A: Aggregation of detergent-insoluble tau is involved in neuronal loss but not in synaptic loss. J Biol Chem. 2010, 285: 38692-38699. 10.1074/jbc.M110.136630.PubMedPubMedCentralCrossRef
78.
Lu DC, Rabizadeh S, Chandra S, Shayya RF, Ellerby LM, Ye X, Salvesen GS, Koo EH, Bredesen DE: A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor. Nat Med. 2000, 6: 397-404. 10.1038/74656.PubMedCrossRef
79.
80.
Hashimoto M, Rockenstein E, Crews L, Masliah E: Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer's and Parkinson's diseases. Neuromolecular Med. 2003, 4: 21-36. 10.1385/NMM:4:1-2:21.PubMedCrossRef
81.
Simoneau S, Rezaei H, Sales N, Kaiser-Schulz G, Lefebvre-Roque M, Vidal C, Fournier JG, Comte J, Wopfner F, Grosclaude J, Schätzl H, Lasmézas CI: In vitro and in vivo neurotoxicity of prion protein oligomers. PLoS Pathog. 2007, 3: e125-10.1371/journal.ppat.0030125.PubMedPubMedCentralCrossRef
82.
de Calignon A, Fox LM, Pitstick R, Carlson GA, Bacskai BJ, Spires-Jones TL, Hyman BT: Caspase activation precedes and leads to tangles. Nature. 464: 1201-1204.
83.
Margittai M, Langen R: Side chain-dependent stacking modulates tau filament structure. J Biol Chem. 2006, 281: 37820-37827. 10.1074/jbc.M605336200.PubMedCrossRef
Metadata
Title
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Authors
Cristian A Lasagna-Reeves
Diana L Castillo-Carranza
Urmi Sengupta
Audra L Clos
George R Jackson
Rakez Kayed
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2011
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-6-39

Other articles of this Issue 1/2011

Molecular Neurodegeneration 1/2011 Go to the issue

Review

Adult hippocampal neurogenesis and its role in Alzheimer's disease

Research article

A glycine zipper motif mediates the formation of toxic β-amyloid oligomers in vitro and in vivo

Research article

Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway

Research article

Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease

Research article

Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

Research article

An organotypic slice culture model of chronic white matter injury with maturation arrest of oligodendrocyte progenitors