Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease (original) (raw)

1. Attwell D, Laughlin SB. An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab. 2001;21:1133–1145. [PubMed] [Google Scholar]

2. Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron. 2005;47:365–378. [PubMed] [Google Scholar]

3. Sun T, Qiao H, Pan PY, Chen Y, Sheng ZH. Motile axonal mitochondria contribute to the variability of presynaptic strength. Cell Rep. 2013;4:413–419. [PMC free article] [PubMed] [Google Scholar]

4. Rangaraju V, Calloway N, Ryan TA. Activity-driven local ATP synthesis is required for synaptic function. Cell. 2014;156:825–835. [PMC free article] [PubMed] [Google Scholar]

5. Gazit N, Vertkin I, Shapira I, Helm M, Slomowitz E, Sheiba M, Mor Y, Rizzoli S, Slutsky I. IGF-1 receptor differentially regulates spontaneous and evoked transmission via mitochondria at hippocampal synapses. Neuron. 2016;89:583–597. [PMC free article] [PubMed] [Google Scholar]

6. Li Z, Okamoto K, Hayashi Y, Sheng M. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell. 2004;119:873–887. [PubMed] [Google Scholar]

7. Lee CW, Peng HB. The function of mitochondria in presynaptic development at the neuromuscular junction. Mol Biol Cell. 2008;19:150–158. [PMC free article] [PubMed] [Google Scholar]

8. Werth JL, Thayer SA. Mitochondria buffer physiological calcium loads in cultured rat dorsal root ganglion neurons. J Neurosci. 1994;14:348–356. [PMC free article] [PubMed] [Google Scholar]

9. Tang Y, Zucker RS. Mitochondrial involvement in post-tetanic potentiation of synaptic transmission. Neuron. 1997;18:483–491. [PubMed] [Google Scholar]

10. Billups B, Forsythe ID. Presynaptic mitochondrial calcium sequestration influences transmission at mammalian central synapses. J Neurosci. 2002;22:5840–5847. [PMC free article] [PubMed] [Google Scholar]

11. David G, Barrett EF. Mitochondrial Ca2+uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals. J Physiol. 2003;548:425–438. [PMC free article] [PubMed] [Google Scholar]

12. Levy M, Faas GC, Saggau P, Craigen WJ, Sweatt JD. Mitochondrial regulation of synaptic plasticity in the hippocampus. J Biol Chem. 2003;278:17727–17734. [PubMed] [Google Scholar]

13. Kang JS, Tian JH, Pan PY, Zald P, Li C, Deng C, Sheng ZH. Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell. 2008;132:137–148. [PMC free article] [PubMed] [Google Scholar]

14. Court FA, Coleman MP. Mitochondria as a central sensor for axonal degenerative stimuli. Trends Neurosci. 2012;35:364–372. [PubMed] [Google Scholar]

15. Sheng ZH, Cai Q. Mitochondrial transport in neurons: Impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci. 2012;13:77–93. [PMC free article] [PubMed] [Google Scholar]

16. Cai Q, Tammineni P. Alterations in mitochondrial quality control in Alzheimer’s disease. Front Cell Neurosci. 2016;10:24. [PMC free article] [PubMed] [Google Scholar]

17. Mishra P, Chan DC. Mitochondrial dynamics and inheritance during cell division, development and disease. Nat Rev Mol Cell Biol. 2014;15:634–646. [PMC free article] [PubMed] [Google Scholar]

18. 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. [PubMed] [Google Scholar]

19. Pettegrew JW, Panchalingam K, Klunk WE, McClure RJ, Muenz LR. Alterations of cerebral metabolism in probable Alzheimer’s disease: A preliminary study. Neurobiol Aging. 1994;15:117–132. [PubMed] [Google Scholar]

20. Duara R, Grady C, Haxby J, Sundaram M, Cutler NR, Heston L, Moore A, Schlageter N, Larson S, Rapoport SI. Positron emission tomography in Alzheimer’s disease. Neurology. 1986;36:879–887. [PubMed] [Google Scholar]

21. Haxby JV, Grady CL, Duara R, Schlageter N, Berg G, Rapoport SI. Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer’s-type dementia. Arch Neurol. 1986;43:882–885. [PubMed] [Google Scholar]

22. Fukui H, Moraes CT. The mitochondrial impairment, oxidative stress and neurodegeneration connection: Reality or just an attractive hypothesis? Trends Neurosci. 2008;31:251–256. [PMC free article] [PubMed] [Google Scholar]

23. Swerdlow RH, Burns JM, Khan SM. The Alzheimer’s disease mitochondrial cascade hypothesis. J Alzheimers Dis. 2010;20(Suppl 2):S265–S279. [PMC free article] [PubMed] [Google Scholar]

24. Sheng ZH. Mitochondrial trafficking and anchoring in neurons: New insight and implications. J Cell Biol. 2014;204:1087–1098. [PMC free article] [PubMed] [Google Scholar]

25. Stock D, Gibbons C, Arechaga I, Leslie AG, Walker JE. The rotary mechanism of ATP synthase. Curr Opin Struct Biol. 2000;10:672–679. [PubMed] [Google Scholar]

26. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A. 1994;91:10771–10778. [PMC free article] [PubMed] [Google Scholar]

27. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239–247. [PubMed] [Google Scholar]

28. Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 2004;427:360–364. [PubMed] [Google Scholar]

29. Crompton M, Virji S, Ward JM. Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore. Eur J Biochem. 1998;258:729–735. [PubMed] [Google Scholar]

30. Halestrap AP, Woodfield KY, Connern CP. Oxidative stress, thiol reagents, and membrane potential modulate the mitochondrial permeability transition by affecting nucleotide binding to the adenine nucleotide translocase. J Biol Chem. 1997;272:3346–3354. [PubMed] [Google Scholar]

31. Connern CP, Halestrap AP. Recruitment of mitochondrial cyclophilin to the mitochondrial inner membrane under conditions of oxidative stress that enhance the opening of a calcium-sensitive non-specific channel. Biochem J. 1994;302(Pt 2):321–324. [PMC free article] [PubMed] [Google Scholar]

32. Bernardi P, Krauskopf A, Basso E, Petronilli V, Blachly-Dyson E, Di Lisa F, Forte MA. The mitochondrial permeability transition from in vitro artifact to disease target. FEBS J. 2006;273:2077–2099. [PubMed] [Google Scholar]

33. Bernardi P. Mitochondrial transport of cations: Channels, exchangers, and permeability transition. Physiol Rev. 1999;79:1127–1155. [PubMed] [Google Scholar]

34. Crompton M. The mitochondrial permeability transition pore and its role in cell death. Biochem J. 1999;341(Pt 2):233–249. [PMC free article] [PubMed] [Google Scholar]

35. Halestrap AP, Kerr PM, Javadov S, Woodfield KY. Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart. Biochim Biophys Acta. 1998;1366:79–94. [PubMed] [Google Scholar]

36. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–629. [PubMed] [Google Scholar]

37. Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281:1309–1312. [PubMed] [Google Scholar]

38. D’Amelio M, Sheng M, Cecconi F. Caspase-3 in the central nervous system: Beyond apoptosis. Trends Neurosci. 2012;35:700–709. [PubMed] [Google Scholar]

39. D’Amelio M, Cavallucci V, Cecconi F. Neuronal caspase-3 signaling: Not only cell death. Cell Death Differ. 2010;17:1104–1114. [PubMed] [Google Scholar]

41. Shepherd GM, Harris KM. Three-dimensional structure and composition of CA3–>CA1 axons in rat hippocampal slices: Implications for presynaptic connectivity and compartmentalization. J Neurosci. 1998;18:8300–8310. [PMC free article] [PubMed] [Google Scholar]

42. Rowland KC, Irby NK, Spirou GA. Specialized synapse-associated structures within the calyx of Held. J Neurosci. 2000;20:9135–9144. [PMC free article] [PubMed] [Google Scholar]

43. Misgeld T, Kerschensteiner M, Bareyre FM, Burgess RW, Lichtman JW. Imaging axonal transport of mitochondria in vivo. Nat Methods. 2007;4:559–561. [PubMed] [Google Scholar]

44. Hurd DD, Saxton WM. Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila. Genetics. 1996;144:1075–1085. [PMC free article] [PubMed] [Google Scholar]

45. Tanaka Y, Kanai Y, Okada Y, Nonaka S, Takeda S, Harada A, Hirokawa N. Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell. 1998;93:1147–1158. [PubMed] [Google Scholar]

46. Cai Q, Gerwin C, Sheng ZH. Syntabulin-mediated anterograde transport of mitochondria along neuronal processes. J Cell Biol. 2005;170:959–969. [PMC free article] [PubMed] [Google Scholar]

47. Pilling AD, Horiuchi D, Lively CM, Saxton WM. Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons. Mol Biol Cell. 2006;17:2057–2068. [PMC free article] [PubMed] [Google Scholar]

48. Gorska-Andrzejak J, Stowers RS, Borycz J, Kostyleva R, Schwarz TL, Meinertzhagen IA. Mitochondria are redistributed in Drosophila photoreceptors lacking milton, a kinesin-associated protein. J Comp Neurol. 2003;463:372–388. [PubMed] [Google Scholar]

49. Stowers RS, Megeath LJ, Gorska-Andrzejak J, Meinertzhagen IA, Schwarz TL. Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron. 2002;36:1063–1077. [PubMed] [Google Scholar]

50. Glater EE, Megeath LJ, Stowers RS, Schwarz TL. Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. J Cell Biol. 2006;173:545–557. [PMC free article] [PubMed] [Google Scholar]

51. MacAskill AF, Brickley K, Stephenson FA, Kittler JT. GTPase dependent recruitment of Grif-1 by Miro1 regulates mitochondrial trafficking in hippocampal neurons. Mol Cell Neurosci. 2009;40:301–312. [PubMed] [Google Scholar]

52. Smith MJ, Pozo K, Brickley K, Stephenson FA. Mapping the GRIF-1 binding domain of the kinesin, KIF5C, substantiates a role for GRIF-1 as an adaptor protein in the anterograde trafficking of cargoes. J Biol Chem. 2006;281:27216–27228. [PubMed] [Google Scholar]

53. Koutsopoulos OS, Laine D, Osellame L, Chudakov DM, Parton RG, Frazier AE, Ryan MT. Human Miltons associate with mitochondria and induce microtubule-dependent remodeling of mitochondrial networks. Biochim Biophys Acta. 2010;1803:564–574. [PubMed] [Google Scholar]

54. Chen Y, Sheng ZH. Kinesin-1-syntaphilin coupling mediates activity-dependent regulation of axonal mitochondrial transport. J Cell Biol. 2013;202:351–364. [PMC free article] [PubMed] [Google Scholar]

55. Brickley K, Stephenson FA. Trafficking kinesin protein (TRAK)-mediated transport of mitochondria in axons of hippocampal neurons. J Biol Chem. 2011;286:18079–18092. [PMC free article] [PubMed] [Google Scholar]

56. Fransson S, Ruusala A, Aspenstrom P. The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking. Biochem Biophys Res Commun. 2006;344:500–510. [PubMed] [Google Scholar]

57. Frederick RL, McCaffery JM, Cunningham KW, Okamoto K, Shaw JM. Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway. J Cell Biol. 2004;167:87–98. [PMC free article] [PubMed] [Google Scholar]

58. Guo X, Macleod GT, Wellington A, Hu F, Panchumarthi S, Schoenfield M, Marin L, Charlton MP, Atwood HL, Zinsmaier KE. The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron. 2005;47:379–393. [PubMed] [Google Scholar]

59. Cho KI, Cai Y, Yi H, Yeh A, Aslanukov A, Ferreira PA. Association of the kinesin-binding domain of RanBP2 to KIF5B and KIF5C determines mitochondria localization and function. Traffic. 2007;8:1722–1735. [PubMed] [Google Scholar]

60. Fujita T, Maturana AD, Ikuta J, Hamada J, Walchli S, Suzuki T, Sawa H, Wooten MW, Okajima T, Tatematsu K, Tanizawa K, Kuroda S. Axonal guidance protein FEZ1 associates with tubulin and kinesin motor protein to transport mitochondria in neurites of NGF-stimulated PC12 cells. Biochem Biophys Res Commun. 2007;361:605–610. [PubMed] [Google Scholar]

61. Russo GJ, Louie K, Wellington A, Macleod GT, Hu F, Panchumarthi S, Zinsmaier KE. Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. J Neurosci. 2009;29:5443–5455. [PMC free article] [PubMed] [Google Scholar]

62. Rintoul GL, Filiano AJ, Brocard JB, Kress GJ, Reynolds IJ. Glutamate decreases mitochondrial size and movement in primary forebrain neurons. J Neurosci. 2003;23:7881–7888. [PMC free article] [PubMed] [Google Scholar]

63. Yi M, Weaver D, Hajnoczky G. Control of mitochondrial motility and distribution by the calcium signal: A homeostatic circuit. J Cell Biol. 2004;167:661–672. [PMC free article] [PubMed] [Google Scholar]

64. Chang DT, Honick AS, Reynolds IJ. Mitochondrial trafficking to synapses in cultured primary cortical neurons. J Neurosci. 2006;26:7035–7045. [PMC free article] [PubMed] [Google Scholar]

65. Ohno N, Kidd GJ, Mahad D, Kiryu-Seo S, Avishai A, Komuro H, Trapp BD. Myelination and axonal electrical activity modulate the distribution and motility of mitochondria at CNS nodes of Ranvier. J Neurosci. 2011;31:7249–7258. [PMC free article] [PubMed] [Google Scholar]

66. Szabadkai G, Simoni AM, Bianchi K, De Stefani D, Leo S, Wieckowski MR, Rizzuto R. Mitochondrial dynamics and Ca2+ signaling. Biochim Biophys Acta. 2006;1763:442–449. [PubMed] [Google Scholar]

67. Macaskill AF, Rinholm JE, Twelvetrees AE, Arancibia-Carcamo IL, Muir J, Fransson A, Aspenstrom P, Attwell D, Kittler JT. Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Neuron. 2009;61:541–555. [PMC free article] [PubMed] [Google Scholar]

68. Saotome M, Safiulina D, Szabadkai G, Das S, Fransson A, Aspenstrom P, Rizzuto R, Hajnoczky G. Bidirectional Ca2+-dependent control of mitochondrial dynamics by the Miro GTPase. Proc Natl Acad Sci U S A. 2008;105:20728–20733. [PMC free article] [PubMed] [Google Scholar]

69. Wang X, Schwarz TL. The mechanism of Ca2+-dependent regulation of kinesin-mediated mitochondrial motility. Cell. 2009;136:163–174. [PMC free article] [PubMed] [Google Scholar]

70. Hubley MJ, Locke BR, Moerland TS. The effects of temperature, pH, and magnesium on the diffusion coefficient of ATP in solutions of physiological ionic strength. Biochim Biophys Acta. 1996;1291:115–121. [PubMed] [Google Scholar]

71. Chen YM, Gerwin C, Sheng ZH. Dynein light chain LC8 regulates syntaphilin-mediated mitochondrial docking in axons. J Neurosci. 2009;29:9429–9438. [PMC free article] [PubMed] [Google Scholar]

72. Ma H, Cai Q, Lu W, Sheng ZH, Mochida S. KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons. J Neurosci. 2009;29:13019–13029. [PMC free article] [PubMed] [Google Scholar]

73. Gibson GE, Shi Q. A mitocentric view of Alzheimer’s disease suggests multi-faceted treatments. J Alzheimers Dis. 2010;20(Suppl 2):S591–S607. [PMC free article] [PubMed] [Google Scholar]

74. Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Pre-clinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996;334:752–758. [PubMed] [Google Scholar]

75. Mosconi L, de Leon M, Murray J, EL, Lu J, Javier E, McHugh P, Swerdlow RH. Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer’s disease. J Alzheimers Dis. 2011;27:483–490. [PMC free article] [PubMed] [Google Scholar]

76. Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF, Kowall N. Oxidative damage in Alzheimer’s. Nature. 1996;382:120–121. [PubMed] [Google Scholar]

77. Maurer I, Zierz S, Moller HJ. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol Aging. 2000;21:455–462. [PubMed] [Google Scholar]

78. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA. Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci. 2001;21:3017–3023. [PMC free article] [PubMed] [Google Scholar]

79. Devi L, Prabhu BM, Galati DF, Avadhani NG, Anandatheerthavarada HK. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer’s disease brain is associated with mitochondrial dysfunction. J Neurosci. 2006;26:9057–9068. [PMC free article] [PubMed] [Google Scholar]

80. Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader JW, Xu HW, Stern D, McKhann G, Yan SD. Mitochondrial Abeta: A potential focal point for neuronal metabolic dysfunction in Alzheimer’s disease. FASEB J. 2005;19:2040–2041. [PubMed] [Google Scholar]

81. Manczak M, Park BS, Jung Y, Reddy PH. Differential expression of oxidative phosphorylation genes in patients with Alzheimer’s disease: Implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med. 2004;5:147–162. [PubMed] [Google Scholar]

82. Manczak M, Calkins MJ, Reddy PH. Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer’s disease: Implications for neuronal damage. Hum Mol Genet. 2011;20:2495–2509. [PMC free article] [PubMed] [Google Scholar]

83. Parker WD, Jr, Filley CM, Parks JK. Cytochrome oxidase deficiency in Alzheimer’s disease. Neurology. 1990;40:1302–1303. [PubMed] [Google Scholar]

84. Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer’s disease brain: Central role for amyloid beta-peptide. Trends Mol Med. 2001;7:548–554. [PubMed] [Google Scholar]

85. Parker WD, Jr, Parks JK. Cytochrome c oxidase in Alzheimer’s disease brain: Purification and characterization. Neurology. 1995;45:482–486. [PubMed] [Google Scholar]

86. Parker WD, Jr, Mahr NJ, Filley CM, Parks JK, Hughes D, Young DA, Cullum CM. Reduced platelet cytochrome c oxidase activity in Alzheimer’s disease. Neurology. 1994;44:1086–1090. [PubMed] [Google Scholar]

87. Cardoso SM, Proenca MT, Santos S, Santana I, Oliveira CR. Cytochrome c oxidase is decreased in Alzheimer’s disease platelets. Neurobiol Aging. 2004;25:105–110. [PubMed] [Google Scholar]

88. Pickrell AM, Fukui H, Moraes CT. The role of cytochrome c oxidase deficiency in ROS and amyloid plaque formation. J Bioenerg Biomembr. 2009;41:453–456. [PubMed] [Google Scholar]

89. Sorbi S, Bird ED, Blass JP. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol. 1983;13:72–78. [PubMed] [Google Scholar]

90. Gibson GE, Blass JP, Beal MF, Bunik V. The alpha-ketoglutarate-dehydrogenase complex: A mediator between mitochondria and oxidative stress in neurodegeneration. Mol Neurobiol. 2005;31:43–63. [PubMed] [Google Scholar]

91. Gibson GE, Zhang H, Sheu KF, Bogdanovich N, Lindsay JG, Lannfelt L, Vestling M, Cowburn RF. Alpha-ketoglutarate dehydrogenase in Alzheimer brains bearing the APP670/671 mutation. Ann Neurol. 1998;44:676–681. [PubMed] [Google Scholar]

92. Lin MT, Simon DK, Ahn CH, Kim LM, Beal MF. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer’s disease brain. Hum Mol Genet. 2002;11:133–145. [PubMed] [Google Scholar]

93. Coskun PE, Beal MF, Wallace DC. Alzheimer’s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci U S A. 2004;101:10726–10731. [PMC free article] [PubMed] [Google Scholar]

94. Coskun PE, Wyrembak J, Derbereva O, Melkonian G, Doran E, Lott IT, Head E, Cotman CW, Wallace DC. Systemic mitochondrial dysfunction and the etiology of Alzheimer’s disease and down syndrome dementia. J Alzheimers Dis. 2010;20(Suppl 2):S293–S310. [PMC free article] [PubMed] [Google Scholar]

95. Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med. 2008;10:291–315. [PMC free article] [PubMed] [Google Scholar]

96. Reddy PH, Beal MF. Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer’s disease. Trends Mol Med. 2008;14:45–53. [PMC free article] [PubMed] [Google Scholar]

97. Reddy PH, McWeeney S, Park BS, Manczak M, Gutala RV, Partovi D, Jung Y, Yau V, Searles R, Mori M, Quinn J. Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: Up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer’s disease. Hum Mol Genet. 2004;13:1225–1240. [PubMed] [Google Scholar]

98. Chandrasekaran K, Giordano T, Brady DR, Stoll J, Martin LJ, Rapoport SI. Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease. Brain Res Mol Brain Res. 1994;24:336–340. [PubMed] [Google Scholar]

99. Manczak M, Jung Y, Park BS, Partovi D, Reddy PH. Time-course of mitochondrial gene expressions in mice brains: Implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging. J Neurochem. 2005;92:494–504. [PubMed] [Google Scholar]

100. Baloyannis SJ. Mitochondrial alterations in Alzheimer’s disease. J Alzheimers Dis. 2006;9:119–126. [PubMed] [Google Scholar]

101. Moreira PI, Siedlak SL, Wang X, Santos MS, Oliveira CR, Tabaton M, Nunomura A, Szweda LI, Aliev G, Smith MA, Zhu X, Perry G. Autophagocytosis of mitochondria is prominent in Alzheimer disease. J Neuropathol Exp Neurol. 2007;66:525–532. [PubMed] [Google Scholar]

102. Trushina E, Nemutlu E, Zhang S, Christensen T, Camp J, Mesa J, Siddiqui A, Tamura Y, Sesaki H, Wengenack TM, Dzeja PP, Poduslo JF. Defects in mitochondrial dynamics and metabolomic signatures of evolving energetic stress in mouse models of familial Alzheimer’s disease. PLoS One. 2012;7:e32737. [PMC free article] [PubMed] [Google Scholar]

103. Reddy PH. Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer’s disease. Brain Res. 2011;1415:136–148. [PMC free article] [PubMed] [Google Scholar]

104. Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer’s amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol. 2003;161:41–54. [PMC free article] [PubMed] [Google Scholar]

105. Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, Bradshaw PC. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer’s transgenic mice. J Alzheimers Dis. 2010;20(Suppl 2):S535–S550. [PubMed] [Google Scholar]

106. Mattson MP, Partin J, Begley JG. Amyloid beta-peptide induces apoptosis-related events in synapses and dendrites. Brain Res. 1998;807:167–176. [PubMed] [Google Scholar]

107. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science. 2004;304:448–452. [PubMed] [Google Scholar]

108. Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med. 2008;14:1097–1105. [PMC free article] [PubMed] [Google Scholar]

109. Manczak M, Mao P, Calkins MJ, Cornea A, Reddy AP, Murphy MP, Szeto HH, Park B, Reddy PH. Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer’s disease neurons. J Alzheimers Dis. 2010;20(Suppl 2):S609–S631. [PMC free article] [PubMed] [Google Scholar]

110. Keller JN, Pang Z, Geddes JW, Begley JG, Germeyer A, Waeg G, Mattson MP. Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: Role of the lipid peroxidation product 4-hydroxynonenal. J Neurochem. 1997;69:273–284. [PubMed] [Google Scholar]

111. Abramov AY, Canevari L, Duchen MR. Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci. 2004;24:565–575. [PMC free article] [PubMed] [Google Scholar]

112. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH. Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet. 2006;15:1437–1449. [PubMed] [Google Scholar]

113. Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci U S A. 2008;105:19318–19323. [PMC free article] [PubMed] [Google Scholar]

114. Manczak M, Reddy PH. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer’s disease neurons: Implications for mitochondrial dysfunction and neuronal damage. Hum Mol Genet. 2012;21:2538–2547. [PMC free article] [PubMed] [Google Scholar]

115. Rui Y, Tiwari P, Xie Z, Zheng JQ. Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons. J Neurosci. 2006;26:10480–10487. [PMC free article] [PubMed] [Google Scholar]

116. Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS. Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc Natl Acad Sci U S A. 2010;107:18670–18675. [PMC free article] [PubMed] [Google Scholar]

117. Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH. Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer’s disease. Hum Mol Genet. 2011;20:4515–4529. [PMC free article] [PubMed] [Google Scholar]

118. Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E, Ankarcrona M. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci U S A. 2008;105:13145–13150. [PMC free article] [PubMed] [Google Scholar]

119. Pinho CM, Teixeira PF, Glaser E. Mitochondrial import and degradation of amyloid-beta peptide. Biochim Biophys Acta. 2014;1837:1069–1074. [PubMed] [Google Scholar]

120. Hedskog L, Pinho CM, Filadi R, Ronnback A, Hertwig L, Wiehager B, Larssen P, Gellhaar S, Sandebring A, Westerlund M, Graff C, Winblad B, Galter D, Behbahani H, Pizzo P, Glaser E, Ankarcrona M. Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer’s disease and related models. Proc Natl Acad Sci U S A. 2013;110:7916–7921. [PMC free article] [PubMed] [Google Scholar]

121. Xie H, Guan J, Borrelli LA, Xu J, Serrano-Pozo A, Bacskai BJ. Mitochondrial alterations near amyloid plaques in an Alzheimer’s disease mouse model. J Neurosci. 2013;33:17042–17051. [PMC free article] [PubMed] [Google Scholar]

122. Mungarro-Menchaca X, Ferrera P, Moran J, Arias C. beta-Amyloid peptide induces ultrastructural changes in synaptosomes and potentiates mitochondrial dysfunction in the presence of ryanodine. J Neurosci Res. 2002;68:89–96. [PubMed] [Google Scholar]

123. Keller JN, Lauderback CM, Butterfield DA, Kindy MS, Yu J, Markesbery WR. Amyloid beta-peptide effects on synaptosomes from apolipoprotein E-deficient mice. J Neurochem. 2000;74:1579–1586. [PubMed] [Google Scholar]

124. D’Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A, Diamantini A, De Zio D, Carrara P, Battistini L, Moreno S, Bacci A, Ammassari-Teule M, Marie H, Cecconi F. Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease. Nat Neurosci. 2011;14:69–76. [PubMed] [Google Scholar]

125. Stokin GB, Goldstein LS. Axonal transport and Alzheimer’s disease. Annu Rev Biochem. 2006;75:607–627. [PubMed] [Google Scholar]

126. Stokin GB, Lillo C, Falzone TL, Brusch RG, Rockenstein E, Mount SL, Raman R, Davies P, Masliah E, Williams DS, Goldstein LS. Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science. 2005;307:1282–1288. [PubMed] [Google Scholar]

127. Pigino G, Morfini G, Pelsman A, Mattson MP, Brady ST, Busciglio J. Alzheimer’s presenilin 1 mutations impair kinesin-based axonal transport. J Neurosci. 2003;23:4499–4508. [PMC free article] [PubMed] [Google Scholar]

128. Detmer SA, Chan DC. Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol. 2007;8:870–879. [PubMed] [Google Scholar]

129. Reddy PH, Reddy TP, Manczak M, Calkins MJ, Shirendeb U, Mao P. Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Res Rev. 2011;67:103–118. [PMC free article] [PubMed] [Google Scholar]

130. Kandimalla R, Reddy PH. Multiple faces of dynamin-related protein 1 and its role in Alzheimer’s disease pathogenesis. Biochim Biophys Acta. 2016;1862:814–828. [PMC free article] [PubMed] [Google Scholar]

131. Chen H, McCaffery JM, Chan DC. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell. 2007;130:548–562. [PubMed] [Google Scholar]

132. Lee S, Sterky FH, Mourier A, Terzioglu M, Cullheim S, Olson L, Larsson NG. Mitofusin 2 is necessary for striatal axonal projections of midbrain dopamine neurons. Hum Mol Genet. 2012;21:4827–4835. [PubMed] [Google Scholar]

133. Pham AH, Meng S, Chu QN, Chan DC. Loss of Mfn2 results in progressive, retrograde degeneration of dopaminergic neurons in the nigrostriatal circuit. Hum Mol Genet. 2012;21:4817–4826. [PMC free article] [PubMed] [Google Scholar]

134. Roy M, Reddy PH, Iijima M, Sesaki H. Mitochondrial division and fusion in metabolism. Curr Opin Cell Biol. 2015;33:111–118. [PMC free article] [PubMed] [Google Scholar]

135. Wang X, Su B, Fujioka H, Zhu X. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer’s disease patients. Am J Pathol. 2008;173:470–482. [PMC free article] [PubMed] [Google Scholar]

136. Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X. Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci. 2009;29:9090–9103. [PMC free article] [PubMed] [Google Scholar]

137. Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L. Tau reduction prevents Abeta-induced defects in axonal transport. Science. 2010;330:198. [PMC free article] [PubMed] [Google Scholar]

138. Wang X, Perry G, Smith MA, Zhu X. Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener Dis. 2010;7:56–59. [PMC free article] [PubMed] [Google Scholar]

139. Zhao XL, Wang WA, Tan JX, Huang JK, Zhang X, Zhang BZ, Wang YH, YangCheng HY, Zhu HL, Sun XJ, Huang FD. Expression of beta-amyloid induced age-dependent presynaptic and axonal changes in Drosophila. J Neurosci. 2010;30:1512–1522. [PMC free article] [PubMed] [Google Scholar]

140. Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ. Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci. 2011;31:6627–6638. [PMC free article] [PubMed] [Google Scholar]

141. Kelly BL, Ferreira A. beta-Amyloid-induced dynamin 1 degradation is mediated by N-methyl-D-aspartate receptors in hippocampal neurons. J Biol Chem. 2006;281:28079–28089. [PubMed] [Google Scholar]

142. Hermann D, Mezler M, Muller MK, Wicke K, Gross G, Draguhn A, Bruehl C, Nimmrich V. Synthetic Abeta oligomers (Abeta(1–42) globulomer) modulate presynaptic calcium currents: Prevention of Abeta-induced synaptic deficits by calcium channel blockers. Eur J Pharmacol. 2013;702:44–55. [PubMed] [Google Scholar]

143. Yagami T, Ueda K, Sakaeda T, Itoh N, Sakaguchi G, Oka-mura N, Hori Y, Fujimoto M. Protective effects of a selective L-type voltage-sensitive calcium channel blocker, S-312-d, on neuronal cell death. Biochem Pharmacol. 2004;67:1153–1165. [PubMed] [Google Scholar]

144. Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K. Amyloid beta protein potentiates Ca2+influx through L-type voltage-sensitive Ca2+channels: A possible involvement of free radicals. J Neurochem. 1997;68:265–271. [PubMed] [Google Scholar]

145. Ferreira IL, Ferreiro E, Schmidt J, Cardoso JM, Pereira CM, Carvalho AL, Oliveira CR, Rego AC. Abeta and NMDAR activation cause mitochondrial dysfunction involving ER calcium release. Neurobiol Aging. 2015;36:680–692. [PubMed] [Google Scholar]

146. Woods NK, Padmanabhan J. Neuronal calcium signaling and Alzheimer’s disease. Adv Exp Med Biol. 2012;740:1193–1217. [PubMed] [Google Scholar]

147. Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL, Hess S, Chan DC. Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet. 2011;20:1726–1737. [PMC free article] [PubMed] [Google Scholar]

148. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell. 2011;147:893–906. [PMC free article] [PubMed] [Google Scholar]

149. Liu S, Sawada T, Lee S, Yu W, Silverio G, Alapatt P, Millan I, Shen A, Saxton W, Kanao T, Takahashi R, Hattori N, Imai Y, Lu B. Parkinson’s disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria. PLoS Genet. 2012;8:e1002537. [PMC free article] [PubMed] [Google Scholar]

150. Cai Q, Zakaria HM, Simone A, Sheng ZH. Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr Biol. 2012;22:545–552. [PMC free article] [PubMed] [Google Scholar]

151. Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014;510:370–375. [PubMed] [Google Scholar]

152. Birsa N, Norkett R, Wauer T, Mevissen TE, Wu HC, Foltynie T, Bhatia K, Hirst WD, Komander D, Plun-Favreau H, Kittler JT. Lysine 27 ubiquitination of the mitochondrial transport protein Miro is dependent on serine 65 of the Parkin ubiquitin ligase. J Biol Chem. 2014;289:14569–14582. [PMC free article] [PubMed] [Google Scholar]

153. Ye X, Sun X, Starovoytov V, Cai Q. Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer’s disease patient brains. Hum Mol Genet. 2015;24:2938–2951. [PMC free article] [PubMed] [Google Scholar]

154. Eckert A, Nisbet R, Grimm A, Gotz J. March separate, strike together–role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer’s disease. Biochim Biophys Acta. 2014;1842:1258–1266. [PubMed] [Google Scholar]

155. Spires-Jones TL, Hyman BT. The intersection of amyloid beta and tau at synapses in Alzheimer’s disease. Neuron. 2014;82:756–771. [PMC free article] [PubMed] [Google Scholar]

156. Schulz KL, Eckert A, Rhein V, Mai S, Haase W, Reichert AS, Jendrach M, Muller WE, Leuner K. A new link to mitochondrial impairment in tauopathies. Mol Neurobiol. 2012;46:205–216. [PubMed] [Google Scholar]

157. Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova NN, Yang L, Starkov AA, Beal F. Behavioral deficit, oxidative stress, and mitochondrial dysfunction precede tau pathology in P301S transgenic mice. FASEB J. 2011;25:4063–4072. [PMC free article] [PubMed] [Google Scholar]

158. Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science. 2001;293:1491–1495. [PubMed] [Google Scholar]

159. David DC, Hauptmann S, Scherping I, Schuessel K, Keil U, Rizzu P, Ravid R, Drose S, Brandt U, Muller WE, Eckert A, Gotz J. Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice. J Biol Chem. 2005;280:23802–23814. [PubMed] [Google Scholar]

160. Manczak M, Reddy PH. Abnormal interaction of VDAC1 with amyloid beta and phosphorylated tau causes mitochondrial dysfunction in Alzheimer’s disease. Hum Mol Genet. 2012;21:5131–5146. [PMC free article] [PubMed] [Google Scholar]

161. Melov S, Adlard PA, Morten K, Johnson F, Golden TR, Hinerfeld D, Schilling B, Mavros C, Masters CL, Volitakis I, Li QX, Laughton K, Hubbard A, Cherny RA, Gibson B, Bush AI. Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS One. 2007;2:e536. [PMC free article] [PubMed] [Google Scholar]

162. Escobar-Khondiker M, Hollerhage M, Muriel MP, Champy P, Bach A, Depienne C, Respondek G, Yamada ES, Lannuzel A, Yagi T, Hirsch EC, Oertel WH, Jacob R, Michel PP, Ruberg M, Hoglinger GU. Annonacin, a natural mitochondrial complex I inhibitor, causes tau pathology in cultured neurons. J Neurosci. 2007;27:7827–7837. [PMC free article] [PubMed] [Google Scholar]

163. DuBoff B, Gotz J, Feany MB. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron. 2012;75:618–632. [PMC free article] [PubMed] [Google Scholar]

164. Quintanilla RA, Dolan PJ, Jin YN, Johnson GV. Truncated tau and Abeta cooperatively impair mitochondria in primary neurons. Neurobiol Aging. 2012;33:619, e625–635. [PMC free article] [PubMed] [Google Scholar]

165. Stamer K, Vogel R, Thies E, Mandelkow E, Mandelkow EM. Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress. J Cell Biol. 2002;156:1051–1063. [PMC free article] [PubMed] [Google Scholar]

166. Dixit R, Ross JL, Goldman YE, Holzbaur EL. Differential regulation of dynein and kinesin motor proteins by tau. Science. 2008;319:1086–1089. [PMC free article] [PubMed] [Google Scholar]

167. Dubey M, Chaudhury P, Kabiru H, Shea TB. Tau inhibits anterograde axonal transport and perturbs stability in growing axonal neurites in part by displacing kinesin cargo: Neurofilaments attenuate tau-mediated neurite instability. Cell Motil Cytoskeleton. 2008;65:89–99. [PubMed] [Google Scholar]

168. LaPointe NE, Morfini G, Pigino G, Gaisina IN, Kozikowski AP, Binder LI, Brady ST. The amino terminus of tau inhibits kinesin-dependent axonal transport: Implications for filament toxicity. J Neurosci Res. 2009;87:440–451. [PMC free article] [PubMed] [Google Scholar]

169. 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. Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport. J Neurochem. 2009;111:417–427. [PMC free article] [PubMed] [Google Scholar]

170. Kanaan NM, Morfini GA, LaPointe NE, Pigino GF, Patterson KR, Song Y, Andreadis A, Fu Y, Brady ST, Binder LI. Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases. J Neurosci. 2011;31:9858–9868. [PMC free article] [PubMed] [Google Scholar]

171. Mufson EJ, Ward S, Binder L. Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer’s disease. Neurodegener Dis. 2014;13:151–153. [PMC free article] [PubMed] [Google Scholar]

172. Vana L, Kanaan NM, Ugwu IC, Wuu J, Mufson EJ, Binder LI. Progression of tau pathology in cholinergic Basal forebrain neurons in mild cognitive impairment and Alzheimer’s disease. Am J Pathol. 2011;179:2533–2550. [PMC free article] [PubMed] [Google Scholar]

173. 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. [PMC free article] [PubMed] [Google Scholar]

174. Kopeikina KJ, Carlson GA, Pitstick R, Ludvigson AE, Peters A, Luebke JI, Koffie RM, Frosch MP, Hyman BT, Spires-Jones TL. Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse model of tauopathy and in human Alzheimer’s disease brain. Am J Pathol. 2011;179:2071–2082. [PMC free article] [PubMed] [Google Scholar]

175. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wolfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Gotz J. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell. 2010;142:387–397. [PubMed] [Google Scholar]

176. Mertens J, Stuber K, Poppe D, Doerr J, Ladewig J, Brustle O, Koch P. Embryonic stem cell-based modeling of tau pathology in human neurons. Am J Pathol. 2013;182:1769–1779. [PubMed] [Google Scholar]

177. Shahpasand K, Uemura I, Saito T, Asano T, Hata K, Shibata K, Toyoshima Y, Hasegawa M, Hisanaga S. Regulation of mitochondrial transport and inter-microtubule spacing by tau phosphorylation at the sites hyperphosphorylated in Alzheimer’s disease. J Neurosci. 2012;32:2430–2441. [PMC free article] [PubMed] [Google Scholar]

178. Gilley J, Seereeram A, Ando K, Mosely S, Andrews S, Kerschensteiner M, Misgeld T, Brion JP, Anderton B, Hanger DP, Coleman MP. Age-dependent axonal transport and locomotor changes and tau hypophosphorylation in a “P301L” tau knockin mouse. Neurobiol Aging. 2012;33:621e621–621e615. [PubMed] [Google Scholar]

179. Iijima-Ando K, Sekiya M, Maruko-Otake A, Ohtake Y, Suzuki E, Lu B, Iijima KM. Loss of axonal mitochondria promotes tau-mediated neurodegeneration and Alzheimer’s disease-related tau phosphorylation via PAR-1. PLoS Genet. 2012;8:e1002918. [PMC free article] [PubMed] [Google Scholar]

180. Crimins JL, Pooler A, Polydoro M, Luebke JI, Spires-Jones TL. The intersection of amyloid beta and tau in glutamatergic synaptic dysfunction and collapse in Alzheimer’s disease. Ageing Res Rev. 2013;12:757–763. [PMC free article] [PubMed] [Google Scholar]

181. Ittner LM, Gotz J. Amyloid-beta and tau–a toxic pas de deux in Alzheimer’s disease. Nat Rev Neurosci. 2011;12:65–72. [PubMed] [Google Scholar]

182. Hardy J. Alzheimer’s disease: The amyloid cascade hypothesis: An update and reappraisal. J Alzheimers Dis. 2006;9:151–153. [PubMed] [Google Scholar]

183. Vossel KA, Xu JC, Fomenko V, Miyamoto T, Suberbielle E, Knox JA, Ho K, Kim DH, Yu GQ, Mucke L. Tau reduction prevents Abeta-induced axonal transport deficits by blocking activation of GSK3beta. J Cell Biol. 2015;209:419–433. [PMC free article] [PubMed] [Google Scholar]

184. Liu X, Hajnoczky G. Ca2+-dependent regulation of mitochondrial dynamics by the Miro-Milton complex. Int J Biochem Cell Biol. 2009;41:1972–1976. [PMC free article] [PubMed] [Google Scholar]

185. Zhou B, Yu P, Lin MY, Sun T, Chen Y, Sheng ZH. Facilitation of axon regeneration by enhancing mitochon-drial transport and rescuing energy deficits. J Cell Biol. 2016;214:103–119. [PMC free article] [PubMed] [Google Scholar]

186. Chen S, Owens GC, Crossin KL, Edelman DB. Serotonin stimulates mitochondrial transport in hippocam-pal neurons. Mol Cell Neurosci. 2007;36:472–483. [PubMed] [Google Scholar]

187. Dumont M, Beal MF. Neuroprotective strategies involving ROS in Alzheimer disease. Free Radic Biol Med. 2011;51:1014–1026. [PMC free article] [PubMed] [Google Scholar]

188. Reddy PH, Tripathi R, Troung Q, Tirumala K, Reddy TP, Anekonda V, Shirendeb UP, Calkins MJ, Reddy AP, Mao P, Manczak M. Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer’s disease: Implications to mitochondria-targeted antioxidant therapeutics. Biochim Biophys Acta. 2012;1822:639–649. [PMC free article] [PubMed] [Google Scholar]