REFERENCES

1. Shrivastava AN, Redeker V, Pieri L, et al. Clustering of Tau fibrils impairs the synaptic composition of α3-Na+/K+-ATPase and AMPA receptors. EMBO J 2019;38:e99871.

2. Vradenburg G. A pivotal moment in Alzheimer’s disease and dementia: how global unity of purpose and action can beat the disease by 2025. Expert Rev Neurother 2015;15:73-82.

3. Taylor CA, Greenlund SF, McGuire LC, Lu H, Croft JB. Deaths from Alzheimer’s Disease - United States, 1999-2014. MMWR Morb Mortal Wkly Rep 2017;66:521-6.

4. Medeiros R, Baglietto-Vargas D, LaFerla FM. The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther 2011;17:514-24.

5. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239-59.

6. Mehta D, Jackson R, Paul G, Shi J, Sabbagh M. Why do trials for Alzheimer’s disease drugs keep failing? A discontinued drug perspective for 2010-2015. Expert Opin Investig Drugs 2017;26:735-9.

7. Dominguez-Meijide A, Vasili E, Outeiro TF. Pharmacological modulators of tau aggregation and spreading. Brain Sci 2020;10:858.

8. Jadhav S, Avila J, Schöll M, et al. A walk through tau therapeutic strategies. Acta Neuropathol Commun 2019;7:22.

9. Imbimbo BP, Balducci C, Ippati S, Watling M. Initial failures of anti-tau antibodies in Alzheimer’s disease are reminiscent of the amyloid-β story. Neural Regen Res 2023;18:117-8.

10. Hanseeuw BJ, Betensky RA, Jacobs HIL, et al. Association of amyloid and tau with cognition in preclinical Alzheimer disease: a longitudinal study. JAMA Neurol 2019;76:915-24.

11. Brier MR, Gordon B, Friedrichsen K, et al. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med 2016;8:338ra66.

12. DiPatre PL, Gelman BB. Microglial cell activation in aging and Alzheimer disease: partial linkage with neurofibrillary tangle burden in the hippocampus. J Neuropathol Exp Neurol 1997;56:143-9.

13. Laurent C, Buée L, Blum D. Tau and neuroinflammation: What impact for Alzheimer’s disease and tauopathies? Biomed J 2018;41:21-33.

14. Malpetti M, Kievit RA, Passamonti L, et al. Microglial activation and tau burden predict cognitive decline in Alzheimer’s disease. Brain 2020;143:1588-602.

15. Pallas-Bazarra N, Draffin J, Cuadros R, Antonio Esteban J, Avila J. Tau is required for the function of extrasynaptic NMDA receptors. Sci Rep 2019;9:9116.

16. Majerova P, Michalicova A, Cente M, et al. Trafficking of immune cells across the blood-brain barrier is modulated by neurofibrillary pathology in tauopathies. PLoS One 2019;14:e0217216.

17. Lantero Rodriguez J, Karikari TK, Suárez-Calvet M, et al. Plasma p-tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline. Acta Neuropathol 2020;140:267-78.

18. Mullard A. Failure of first anti-tau antibody in Alzheimer disease highlights risks of history repeating. Nat Rev Drug Discov 2021;20:3-5.

19. Salloway SP, Sevingy J, Budur K, et al. Advancing combination therapy for Alzheimer’s disease. Alzheimers Dement 2020;6:e12073.

20. González JF, Alcántara AR, Doadrio AL, Sánchez-Montero JM. Developments with multi-target drugs for Alzheimer’s disease: an overview of the current discovery approaches. Expert Opin Drug Discov 2019;14:879-91.

21. Michel CH, Kumar S, Pinotsi D, et al. Extracellular monomeric tau protein is sufficient to initiate the spread of tau protein pathology. J Biol Chem 2014;289:956-67.

22. Nykänen NP, Kysenius K, Sakha P, Tammela P, Huttunen HJ. γ-Aminobutyric acid type A (GABAA) receptor activation modulates tau phosphorylation. J Biol Chem 2012;287:6743-52.

23. Neddens J, Temmel M, Flunkert S, et al. Phosphorylation of different tau sites during progression of Alzheimer’s disease. Acta Neuropathol Commun 2018;6:52.

24. Maphis N, Xu G, Kokiko-Cochran ON, et al. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain 2015;138:1738-55.

25. Martini-Stoica H, Cole AL, Swartzlander DB, et al. TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading. J Exp Med 2018;215:2355-77.

26. Zhang K, Sun Z, Chen X, Zhang Y, Guo A, Zhang Y. Intercellular transport of Tau protein and β-amyloid mediated by tunneling nanotubes. Am J Transl Res 2021;13:12509-22.

27. Henschel O, Gipson KE, Bordey A. GABAA receptors, anesthetics and anticonvulsants in brain development. CNS Neurol Disord Drug Targets 2008;7:211-24.

28. Slomski A. Anti-tau antibody semorinemab fails to slow Alzheimer disease. JAMA 2022;328:415.

29. Banks WA. Characteristics of compounds that cross the blood-brain barrier. BMC Neurol 2009;9 Suppl 1:S3.

30. Pardridge WM. Treatment of Alzheimer’s disease and blood-brain barrier drug delivery. Pharmaceuticals 2020;13:394.

31. DeVos SL, Corjuc BT, Commins C, et al. Tau reduction in the presence of amyloid-β prevents tau pathology and neuronal death in vivo. Brain 2018;141:2194-212.

32. Mummery CJ, Börjesson-Hanson A, Blackburn DJ, et al. Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial. Nat Med 2023;29:1437-47.

33. Mignon L, Kordasiewicz H, Lane R, et al. Design of the first-in-human study of IONIS-MAPTRx, a tau-lowering antisense oligonucleotide, in patients with Alzheimer disease (S2.006). 2018;90:S2.006. Available from: https://www.neurology.org/doi/10.1212/WNL.90.15_supplement.S2.006. [Last accessed on 26 Oct 2023].

34. Imbimbo BP, Ippati S, Watling M, Balducci C. A critical appraisal of tau-targeting therapies for primary and secondary tauopathies. Alzheimers Dement 2022;18:1008-37.

35. Edwards Z, Preuss CV. GABA receptor positive allosteric modulators. In StatPearls, StatPearls Publishing 2023.

36. Amaral AC, Perez-Nievas BG, Siao Tick Chong M, et al. Isoform-selective decrease of glycogen synthase kinase-3-beta (GSK-3β) reduces synaptic tau phosphorylation, transcellular spreading, and aggregation. iScience 2021;24:102058.

37. Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 2000;406:86-90.

38. Leclair-Visonneau L, Rouaud T, Debilly B, et al. Randomized placebo-controlled trial of sodium valproate in progressive supranuclear palsy. Clin Neurol Neurosurg 2016;146:35-9.

39. Wang H, Huang S, Yan K, et al. Tideglusib, a chemical inhibitor of GSK3β, attenuates hypoxic-ischemic brain injury in neonatal mice. Biochim Biophys Acta 2016;1860:2076-85.

40. Lovestone S, Boada M, Dubois B, et al. A phase II trial of tideglusib in Alzheimer’s disease. J Alzheimers Dis 2015;45:75-88.

41. Kanekiyo T, Zhang J, Liu Q, Liu CC, Zhang L, Bu G. Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-beta uptake. J Neurosci 2011;31:1644-51.

42. Shinohara M, Tachibana M, Kanekiyo T, Bu G. Role of LRP1 in the pathogenesis of Alzheimer’s disease: evidence from clinical and preclinical studies. J Lipid Res 2017;58:1267-81.

43. Rauch JN, Luna G, Guzman E, et al. LRP1 is a master regulator of tau uptake and spread. Nature 2020;580:381-5.

44. Evans LD, Wassmer T, Fraser G, et al. Extracellular monomeric and aggregated tau efficiently enter human neurons through overlapping but distinct pathways. Cell Rep 2018;22:3612-24.

45. Holmes BB, DeVos SL, Kfoury N, et al. Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci U S A 2013;110:E3138-47.

46. Pooler AM, Phillips EC, Lau DH, Noble W, Hanger DP. Physiological release of endogenous tau is stimulated by neuronal activity. EMBO Rep 2013;14:389-94.

47. Edwards IJ, Bruce G, Lawrenson C, et al. Na+/K+ ATPase α1 and α3 isoforms are differentially expressed in α- and γ-motoneurons. J Neurosci 2013;33:9913-9.

48. Tardivel M, Bégard S, Bousset L, et al. Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies. Acta Neuropathol Commun 2016;4:117.

49. Gousset K, Marzo L, Commere PH, Zurzolo C. Myo10 is a key regulator of TNT formation in neuronal cells. J Cell Sci 2013;126:4424-35.

50. Bond LM, Tumbarello DA, Kendrick-Jones J, Buss F. Small-molecule inhibitors of myosin proteins. Future Med Chem 2013;5:41-52.

51. Dilsizoglu Senol A, Pepe A, Grudina C, et al. Effect of tolytoxin on tunneling nanotube formation and function. Sci Rep 2019;9:5741.

52. Asai H, Ikezu S, Tsunoda S, et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci 2015;18:1584-93.

53. Shum LC, White NS, Nadtochiy SM, et al. Cyclophilin D knock-out mice show enhanced resistance to osteoporosis and to metabolic changes observed in aging bone. PLoS One 2016;11:e0155709.

54. Costa-Mattioli M, Walter P. The integrated stress response: from mechanism to disease. Science 2020;368:eaat5314.

55. Lu T, Pan Y, Kao SY, et al. Gene regulation and DNA damage in the ageing human brain. Nature 2004;429:883-91.

56. Méndez D, Arauna D, Fuentes F, et al. Mitoquinone (MitoQ) inhibits platelet activation steps by reducing ROS levels. Int J Mol Sci 2020;21:6192.

57. Maggiore A, Casale AM, Toscanelli W, et al. Neuroprotective effects of PARP inhibitors in drosophila models of Alzheimer’s disease. Cells 2022;11:1284.

58. Song L, Oseid DE, Wells EA, Coaston T, Robinson AS. Heparan sulfate proteoglycans (HSPGs) serve as the mediator between monomeric tau and its subsequent intracellular ERK1/2 pathway activation. J Mol Neurosci 2022;72:772-91.

59. Xu H, Rösler TW, Carlsson T, et al. Tau silencing by siRNA in the P301S mouse model of tauopathy. Curr Gene Ther 2014;14:343-51.

60. Le Guennec K, Quenez O, Nicolas G, et al. 17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression. Mol Psychiatry 2017;22:1119-25.

61. Schoch KM, DeVos SL, Miller RL, et al. Increased 4R-tau induces pathological changes in a human-tau mouse model. Neuron 2016;90:941-7.

62. Soeda Y, Takashima A. New insights into drug discovery targeting tau protein. Front Mol Neurosci 2020;13:590896.

63. Lei P, Ayton S, Appukuttan AT, et al. Lithium suppression of tau induces brain iron accumulation and neurodegeneration. Mol Psychiatry 2017;22:396-406.

64. Lei P, Ayton S, Finkelstein DI, et al. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med 2012;18:291-5.

65. Lopes S, Lopes A, Pinto V, et al. Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits and motor impairment. Aging Cell 2016;15:208-16.

66. Sapir T, Frotscher M, Levy T, Mandelkow EM, Reiner O. Tau’s role in the developing brain: implications for intellectual disability. Hum Mol Genet 2012;21:1681-92.

67. Pallas-Bazarra N, Jurado-Arjona J, Navarrete M, et al. Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis. EMBO J 2016;35:1417-36.

68. Kim J, de Haro M, Al-Ramahi I, et al. Evolutionarily conserved regulators of tau identify targets for new therapies. Neuron 2023;111:824-38.e7.

69. Min SW, Cho SH, Zhou Y, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 2010;67:953-66.

70. Min SW, Chen X, Tracy TE, et al. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat Med 2015;21:1154-62.

71. Trzeciakiewicz H, Tseng JH, Wander CM, et al. A dual pathogenic mechanism links tau acetylation to sporadic tauopathy. Sci Rep 2017;7:44102.

72. Jiang S, Sydney EJ, Runyan AM, et al. 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy. bioRxiv 2023; In press.

73. Cruz MP. Vilazodone HCl (Viibryd): a serotonin partial agonist and reuptake inhibitor for the treatment of major depressive disorder. P T 2012;37:28-31.

74. Serotonin 5-HT4 Receptor Agonists. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury; 2019.

75. Sandhu P, Lee J, Ballard J, et al. P4-036: pharmacokinetics and pharmacodynamics to support clinical studies of MK-8719: an O-glcnacase inhibitor for progressive supranuclear palsy. Alzheimers Dement 2016;12:P1028.

76. Ryan JM, Quattropani A, Abd-elaziz K, et al. O1-12-05: phase 1 study in healthy volunteers of the o-glcnacase inhibitor asn120290 as a novel therapy for progressive supranuclear palsy and related tauopathies. Alzheimers Dement 2018;14:P251.

77. Kielbasa W, Phipps KM, Tseng J, et al. A single ascending dose study in healthy volunteers to assess the safety and PK of LY3372689, an inhibitor of O-GlcNAcase (OGA) enzyme: Human/Human trials: Anti-tau. Alzheimers Dement 2020;16:e040473.

78. Gauthier S, Feldman HH, Schneider LS, et al. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer’s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 2016;388:2873-84.

79. Wilcock GK, Gauthier S, Frisoni GB, et al. Potential of low dose leuco-methylthioninium bis(hydromethanesulphonate) (LMTM) monotherapy for treatment of mild Alzheimer’s disease: cohort analysis as modified primary outcome in a phase III clinical trial. J Alzheimers Dis 2018;61:435-57.

80. Soeda Y, Saito M, Maeda S, et al. Methylene blue inhibits formation of tau fibrils but not of granular tau oligomers: a plausible key to understanding failure of a clinical trial for Alzheimer’s disease. J Alzheimers Dis 2019;68:1677-86.

81. Li Y, Sun H, Chen Z, Xu H, Bu G, Zheng H. Implications of GABAergic neurotransmission in Alzheimer’s disease. Front Aging Neurosci 2016;8:31.

82. Arnold CS, Johnson GV, Cole RN, Dong DL, Lee M, Hart GW. The microtubule-associated protein tau is extensively modified with O-linked N-acetylglucosamine. J Biol Chem 1996;271:28741-4.

83. Liu F, Iqbal K, Grundke-Iqbal I, Hart GW, Gong CX. O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer’s disease. Proc Natl Acad Sci U S A 2004;101:10804-9.

84. Hart GW, Housley MP, Slawson C. Cycling of O-linked beta-N-acetylglucosamine on nucleocytoplasmic proteins. Nature 2007;446:1017-22.

85. Zhang H, Cao Y, Ma L, Wei Y, Li H. Possible mechanisms of tau spread and toxicity in Alzheimer’s disease. Front Cell Dev Biol 2021;9:707268.

86. Gong CX, Grundke-Iqbal I, Iqbal K. Dephosphorylation of Alzheimer’s disease abnormally phosphorylated tau by protein phosphatase-2A. Neuroscience 1994;61:765-72.

87. Whittington RA, Bretteville A, Dickler MF, Planel E. Anesthesia and tau pathology. Prog Neuropsychopharmacol Biol Psychiatry 2013;47:147-55.

88. Kozikowski AP, Gaisina IN, Petukhov PA, et al. Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson’s disease. ChemMedChem 2006;1:256-66.

89. Mines MA, Beurel E, Jope RS. Regulation of cell survival mechanisms in Alzheimer’s disease by glycogen synthase kinase-3. Int J Alzheimers Dis 2011;2011:861072.

90. Kimura T, Tsutsumi K, Taoka M, et al. Isomerase Pin1 stimulates dephosphorylation of tau protein at cyclin-dependent kinase (Cdk5)-dependent Alzheimer phosphorylation sites. J Biol Chem 2013;288:7968-77.

91. Yasuno F, Minami H. Significant effects of cholinesterase inhibitors on tau pathology in the Alzheimer’s disease continuum: An in vivo positron emission tomography study. Int J Geriatr Psychiatry 2021;36:1274-83.

92. Cripps D, Thomas SN, Jeng Y, Yang F, Davies P, Yang AJ. Alzheimer disease-specific conformation of hyperphosphorylated paired helical filament-Tau is polyubiquitinated through Lys-48, Lys-11, and Lys-6 ubiquitin conjugation. J Biol Chem 2006;281:10825-38.

93. VandeVrede L, Dale ML, Fields S, et al. Open-label phase 1 futility studies of salsalate and young plasma in progressive supranuclear palsy. Mov Disord Clin Pract 2020;7:440-7.

94. Mukadam AS, Miller LVC, Smith AE, et al. Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models. Science 2023;379:1336-41.

95. Foss S, Bottermann M, Jonsson A, Sandlie I, James LC, Andersen JT. TRIM21-from intracellular immunity to therapy. Front Immunol 2019;10:2049.

96. Domenico F, Lanzillotta C, Tramutola A. Therapeutic potential of rescuing protein O-GlcNAcylation in tau-related pathologies. Expert Rev Neurother 2019;19:1-3.

97. Kim S, Lim K, Yang S, Joo J. Boosting of tau protein aggregation by CD40 and CD48 gene expression in Alzheimer’s disease. FASEB J 2023;37:e22702.

98. Mao X, Ou MT, Karuppagounder SS, et al. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science 2016;353:aah3374.

99. Woo SR, Li N, Bruno TC, et al. Differential subcellular localization of the regulatory T-cell protein LAG-3 and the coreceptor CD4. Eur J Immunol 2010;40:1768-77.

100. Workman C, Rice D, Dugger K, Kurschner C, Vignali D. Phenotypic analysis of the murine CD4-related glycoprotein, CD223 (LAG-3). Eur J Immunol 2002;32:2255-63.

101. Tachibana M, Holm ML, Liu CC, et al. APOE4-mediated amyloid-β pathology depends on its neuronal receptor LRP1. J Clin Invest 2019;129:1272-7.

102. Horonchik L, Tzaban S, Ben-Zaken O, et al. Heparan sulfate is a cellular receptor for purified infectious prions. J Biol Chem 2005;280:17062-7.

103. Schonberger O, Horonchik L, Gabizon R, Papy-Garcia D, Barritault D, Taraboulos A. Novel heparan mimetics potently inhibit the scrapie prion protein and its endocytosis. Biochem Biophys Res Commun 2003;312:473-9.

104. Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol 2011;3:a004952.

105. Cui X, Xie Z. Protein interaction and Na/K-ATPase-mediated signal transduction. Molecules 2017;22:990.

106. Chater TE, Goda Y. The role of AMPA receptors in postsynaptic mechanisms of synaptic plasticity. Front Cell Neurosci 2014;8:401.

107. Kaplan IM, Wadia JS, Dowdy SF. Cationic TAT peptide transduction domain enters cells by macropinocytosis. J Control Release 2005;102:247-53.

108. Wadia JS, Stan RV, Dowdy SF. Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis. Nat Med 2004;10:310-5.

109. Chiroma SM, Baharuldin MTH, Taib CNM, Amom Z, Jagadeesan S, Moklas MAM. Inflammation in Alzheimer’s disease: a friend or foe? Biomedical Research and Therapy 2018;5:2552-64.

110. Chen C, Kumbhar R, Wang H, et al. Pathological tau transmission initiated by binding lymphocyte-activation gene 3. bioRxiv 2023.

111. Rauch JN, Chen JJ, Sorum AW, et al. Tau internalization is regulated by 6-O sulfation on heparan sulfate proteoglycans (HSPGs). Sci Rep 2018;8:6382.

112. Chen K, Martens YA, Meneses A, et al. LRP1 is a neuronal receptor for α-synuclein uptake and spread. Mol Neurodegener 2022;17:57.

113. Gu H, Yang X, Mao X, et al. Lymphocyte activation gene 3 (Lag3) contributes to α-synucleinopathy in α-synuclein transgenic mice. Front Cell Neurosci 2021;15:656426.

114. Zhang S, Liu YQ, Jia C, et al. Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson’s disease. 2021;118:e2011196118.

115. Morris M, Maeda S, Vossel K, Mucke L. The many faces of tau. Neuron 2011;70:410-26.

116. Hanger DP, Anderton BH, Noble W. Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 2009;15:112-9.

117. Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 1992;359:832-5.

118. Lago J, Rodríguez LP, Blanco L, Vieites JM, Cabado AG. Tetrodotoxin, an extremely potent marine neurotoxin: distribution, toxicity, origin and therapeutical uses. Mar Drugs 2015;13:6384-406.

119. Chalmers KA, Wilcock GK, Vinters HV, et al. Cholinesterase inhibitors may increase phosphorylated tau in Alzheimer’s disease. J Neurol 2009;256:717-20.

120. Hellström-Lindahl E, Moore H, Nordberg A. Increased levels of tau protein in SH-SY5Y cells after treatment with cholinesterase inhibitors and nicotinic agonists. J Neurochem 2000;74:777-84.

121. Allcock RJ, Barrow AD, Forbes S, Beck S, Trowsdale J. The human TREM gene cluster at 6p21.1 encodes both activating and inhibitory single IgV domain receptors and includes NKp44. Eur J Immunol 2003;33:567-77.

122. Gratuze M, Leyns CEG, Holtzman DM. New insights into the role of TREM2 in Alzheimer’s disease. Mol Neurodegener 2018;13:66.

123. Turnbull IR, Gilfillan S, Cella M, et al. Cutting edge: TREM-2 attenuates macrophage activation. J Immunol 2006;177:3520-4.

124. Li Y, Xu H, Wang H, Yang K, Luan J, Wang S. TREM2: potential therapeutic targeting of microglia for Alzheimer's disease. Biomed Pharmacother 2023;165:115218.

125. Cheng Q, Danao J, Talreja S, et al. TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer’s disease variant Trem2R47H on murine myeloid cell function. J Biol Chem 2018;293:12620-33.

126. Wang C, Fan L, Khawaja RR, et al. Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy. Nat Commun 2022;13:1969.

127. Cui JG, Hill JM, Zhao Y, Lukiw WJ. Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer’s disease. Neuroreport 2007;18:115-9.

128. Lukiw WJ. Gene expression profiling in fetal, aged, and Alzheimer hippocampus: a continuum of stress-related signaling. Neurochem Res 2004;29:1287-97.

129. Polito VA, Li H, Martini-Stoica H, et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol Med 2014;6:1142-60.

130. Lu Y, Chen X, Liu X, et al. Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction. Autophagy 2023;19:1803-20.

131. Park JS, Kam TI, Lee S, et al. Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer’s disease. Acta Neuropathol Commun 2021;9:78.

132. Hansen HH, Barkholt P, Fabricius K, et al. The GLP-1 receptor agonist liraglutide reduces pathology-specific tau phosphorylation and improves motor function in a transgenic hTauP301L mouse model of tauopathy. Brain Res 2016;1634:158-70.

133. Xu W, Yang Y, Yuan G, Zhu W, Ma D, Hu S. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces Alzheimer disease-associated tau hyperphosphorylation in the hippocampus of rats with type 2 diabetes. J Investig Med 2015;63:267-72.

134. Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med 2017;23:512-33.

135. Leyns CEG, Gratuze M, Narasimhan S, et al. TREM2 function impedes tau seeding in neuritic plaques. Nat Neurosci 2019;22:1217-22.

136. Perez SE, Nadeem M, He B, et al. Neocortical and hippocampal TREM2 protein levels during the progression of Alzheimer’s disease. Neurobiol Aging 2017;54:133-43.

137. Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res 2002;70:462-73.

138. Ghosh S, Wu MD, Shaftel SS, et al. Sustained interleukin-1β overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer’s mouse model. J Neurosci 2013;33:5053-64.

139. Parkhurst CN, Yang G, Ninan I, et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 2013;155:1596-609.

140. Panatier A, Vallée J, Haber M, Murai KK, Lacaille JC, Robitaille R. Astrocytes are endogenous regulators of basal transmission at central synapses. Cell 2011;146:785-98.

141. Chever O, Dossi E, Pannasch U, Derangeon M, Rouach N. Astroglial networks promote neuronal coordination. Sci Signal 2016;9:ra6.

142. Henstridge CM, Tzioras M, Paolicelli RC. Glial contribution to excitatory and inhibitory synapse loss in neurodegeneration. Front Cell Neurosci 2019;13:63.

143. Grimaldi A, Pediconi N, Oieni F, et al. Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer’s disease patients, possible biomarkers for early diagnosis. Front Neurosci 2019;13:925.

144. Stadelmann C, Kerschensteiner M, Misgeld T, Brück W, Hohlfeld R, Lassmann H. BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 2002;125:75-85.

145. Farina C, Aloisi F, Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol 2007;28:138-45.

146. Lian H, Yang L, Cole A, et al. NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer’s disease. Neuron 2015;85:101-15.

147. Sardiello M, Palmieri M, di Ronza A, et al. A gene network regulating lysosomal biogenesis and function. Science 2009;325:473-7.

148. Yanamandra K, Kfoury N, Jiang H, et al. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Neuron 2013;80:402-14.

149. Holmes BB, Furman JL, Mahan TE, et al. Proteopathic tau seeding predicts tauopathy in vivo. Proc Natl Acad Sci U S A 2014;111:E4376-85.

150. Athauda D, Foltynie T. The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson’s disease: mechanisms of action. Drug Discov Today 2016;21:802-18.

151. Tweedie D, Rachmany L, Rubovitch V, et al. Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4. Alzheimers Dement 2016;12:34-48.

152. Chen S, An FM, Yin L, et al. Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation. Neuroscience 2014;256:137-46.

153. Yun SP, Kam TI, Panicker N, et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease. Nat Med 2018;24:931-8.

154. Liddelow SA, Guttenplan KA, Clarke LE, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 2017;541:481-7.

155. Eugenin EA, Gaskill PJ, Berman JW. Tunneling nanotubes (TNT) are induced by HIV-infection of macrophages: a potential mechanism for intercellular HIV trafficking. Cell Immunol 2009;254:142-8.

156. Abounit S, Wu JW, Duff K, Victoria GS, Zurzolo C. Tunneling nanotubes: a possible highway in the spreading of tau and other prion-like proteins in neurodegenerative diseases. Prion 2016;10:344-51.

157. Wang Y, Balaji V, Kaniyappan S, et al. The release and trans-synaptic transmission of Tau via exosomes. Mol Neurodegener 2017;12:5.

158. Yin Q, Ji X, Lv R, et al. Targetting exosomes as a new biomarker and therapeutic approach for Alzheimer’s disease. Clin Interv Aging 2020;15:195-205.

159. Kalra H, Drummen GP, Mathivanan S. Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci 2016;17:170.

160. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007;9:654-9.

161. Fevrier B, Vilette D, Archer F, et al. Cells release prions in association with exosomes. Proc Natl Acad Sci U S A 2004;101:9683-8.

162. Lee Y, El Andaloussi S, Wood MJ. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 2012;21:R125-34.

163. Xu X, Colombini M. Autodirected insertion: preinserted VDAC channels greatly shorten the delay to the insertion of new channels. Biophys J 1997;72:2129-36.

164. Hodge T, Colombini M. Regulation of metabolite flux through voltage-gating of VDAC channels. J Membr Biol 1997;157:271-9.

165. Colombini M. VDAC structure, selectivity, and dynamics. Biochim Biophys Acta 2012;1818:1457-65.

166. 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;21:5131-46.

167. Raghavan A, Sheiko T, Graham BH, Craigen WJ. Voltage-dependant anion channels: novel insights into isoform function through genetic models. Biochim Biophys Acta 2012;1818:1477-85.

168. 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;20:2495-509.

169. Du H, Guo L, Fang F, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med 2008;14:1097-105.

170. Harding HP, Zhang Y, Zeng H, et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 2003;11:619-33.

171. Birnbaum JH, Wanner D, Gietl AF, et al. Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer’s disease patients. Stem Cell Res 2018;27:121-30.

172. Samluk L, Ostapczuk P, Dziembowska M. Long-term mitochondrial stress induces early steps of tau aggregation by increasing reactive oxygen species levels and affecting cellular proteostasis. Mol Biol Cell 2022;33:ar67.

173. Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res 2013;8:2003-14.

174. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006;443:787-95.

175. Ahmadi S, Zhu S, Sharma R, et al. Aggregation of Microtubule Binding Repeats of Tau Protein is Promoted by Cu2+. ACS Omega 2019;4:5356-66.

176. Gaubert S, Bouchaut M, Brumas V, Berthon G. Copper - ligand interactions and the physiological free radical processes. Part 3. Influence of histidine, salicylic acid and anthranilic acid on copper-driven Fenton chemistry in vitro. Free Radic Res 2000;32:451-61.

177. Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N Engl J Med 1997;336:1216-22.

178. Morris MC, Evans DA, Bienias JL, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA 2002;287:3230-7.

179. Pritam P, Deka R, Bhardwaj A, et al. Antioxidants in Alzheimer’s disease: current therapeutic significance and future prospects. Biology 2022;11:212.

180. Kong D, Yan Y, He XY, et al. Effects of resveratrol on the mechanisms of antioxidants and estrogen in Alzheimer’s disease. Biomed Res Int 2019;2019:8983752.

181. Wei QY, Chen WF, Zhou B, Yang L, Liu ZL. Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim Biophys Acta 2006;1760:70-7.

182. Haque AM, Hashimoto M, Katakura M, Hara Y, Shido O. Green tea catechins prevent cognitive deficits caused by Abeta1-40 in rats. J Nutr Biochem 2008;19:619-26.

183. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimers Dis 2004;6:367-77; discussion 443-9.

184. Serafini MM, Catanzaro M, Rosini M, Racchi M, Lanni C. Curcumin in Alzheimer’s disease: can we think to new strategies and perspectives for this molecule? Pharmacol Res 2017;124:146-55.

185. Seo JS, Kim TK, Leem YH, et al. SK-PC-B70M confers anti-oxidant activity and reduces Abeta levels in the brain of Tg2576 mice. Brain Res 2009;1261:100-8.

186. Quinn JF, Bussiere JR, Hammond RS, et al. Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiol Aging 2007;28:213-25.

187. Sajjad N, Wani A, Hassan S, et al. Interplay of antioxidants in Alzheimer’s disease. Available from: https://www.oatext.com/interplay-of-antioxidants-in-alzheimers-disease.php. [Last accessed on 26 Oct 2023].

188. Maas T, Eidenmüller J, Brandt R. Interaction of tau with the neural membrane cortex is regulated by phosphorylation at sites that are modified in paired helical filaments. J Biol Chem 2000;275:15733-40.

189. Kar S, Fan J, Smith MJ, Goedert M, Amos LA. Repeat motifs of tau bind to the insides of microtubules in the absence of taxol. EMBO J 2003;22:70-7.

190. Tsai RM, Miller Z, Koestler M, et al. Reactions to multiple ascending doses of the microtubule stabilizer TPI-287 in patients with Alzheimer disease, progressive supranuclear palsy, and corticobasal syndrome: a randomized clinical trial. JAMA Neurol 2020;77:215-24.

191. Morimoto BH, Schmechel D, Hirman J, Blackwell A, Keith J, Gold M. AL-108-211 Study. A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment. Dement Geriatr Cogn Disord 2013;35:325-36.

192. Nicholls SB, DeVos SL, Commins C, et al. Characterization of TauC3 antibody and demonstration of its potential to block tau propagation. PLoS One 2017;12:e0177914.

193. Zhao X, Kotilinek LA, Smith B, et al. Caspase-2 cleavage of tau reversibly impairs memory. Nat Med 2016;22:1268-76.

194. Hoover BR, Reed MN, Su J, et al. Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 2010;68:1067-81.

195. Nalabothula N, Al-jumaily T, Eteleeb AM, et al. Genome-wide profiling of PARP1 reveals an interplay with gene regulatory regions and DNA methylation. PLoS One 2015;10:e013540.

196. Poirier GG, de Murcia G, Jongstra-Bilen J, Niedergang C, Mandel P. Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci U S A 1982;79:3423-7.

197. d'Erme M, Yang G, Sheagly E, Palitti F, Bustamante C. Effect of poly(ADP-ribosyl)ation and Mg2+ ions on chromatin structure revealed by scanning force microscopy. Biochemistry 2001;40:10947-55.

198. Messner S, Altmeyer M, Zhao H, et al. PARP1 ADP-ribosylates lysine residues of the core histone tails. Nucleic Acids Res 2010;38:6350-62.

199. Krishnakumar R, Gamble MJ, Frizzell KM, Berrocal JG, Kininis M, Kraus WL. Reciprocal binding of PARP-1 and histone H1 at promoters specifies transcriptional outcomes. Science 2008;319:819-21.

200. De Vos M, Schreiber V, Dantzer F. The diverse roles and clinical relevance of PARPs in DNA damage repair: current state of the art. Biochem Pharmacol 2012;84:137-46.

201. Bürkle A, Virág L. Poly(ADP-ribose): PARadigms and PARadoxes. Mol Aspects Med 2013;34:1046-65.

202. Halappanavar SS, Shah GM. Defective control of mitotic and post-mitotic checkpoints in poly(ADP-ribose) polymerase-1(-/-) fibroblasts after mitotic spindle disruption. Cell Cycle 2003;3:333-40.

203. Liu S, Luo W, Wang Y. Emerging role of PARP-1 and PARthanatos in ischemic stroke. J Neurochem 2022;160:74-87.

204. Wells JN, Feschotte C. A field guide to eukaryotic transposable elements. Annu Rev Genet 2020;54:539-61.

205. Gandini A, Bartolini M, Tedesco D, et al. Tau-centric multitarget approach for Alzheimer’s disease: development of first-in-class dual glycogen synthase kinase 3β and tau-aggregation inhibitors. J Med Chem 2018;61:7640-56.

206. Prati F, De Simone A, Bisignano P, et al. Multitarget drug discovery for Alzheimer’s disease: triazinones as BACE-1 and GSK-3β inhibitors. Angew Chem Int Ed Engl 2015;54:1578-82.

207. La-Rocque S, Moretto E, Butnaru I, Schiavo G. Knockin’ on heaven’s door: molecular mechanisms of neuronal tau uptake. J Neurochem 2021;156:563-88.

208. Pardridge WM. CSF, blood-brain barrier, and brain drug delivery. Expert Opin Drug Deliv 2016;13:963-75.

209. Xu J, Du W, Zhao Y, et al. Mitochondria targeting drugs for neurodegenerative diseases-Design, mechanism and application. Acta Pharm Sin B 2022;12:2778-89.

210. Nitzan K, Benhamron S, Valitsky M, et al. Mitochondrial transfer ameliorates cognitive deficits, neuronal loss, and gliosis in Alzheimer’s disease mice. J Alzheimers Dis 2019;72:587-604.

211. Ossenkoppele R, Smith R, Mattsson-Carlgren N, et al. Accuracy of tau positron emission tomography as a prognostic marker in preclinical and prodromal Alzheimer disease: a head-to-head comparison against amyloid positron emission tomography and magnetic resonance imaging. JAMA Neurol 2021;78:961-71.

212. Lagarde J, Olivieri P, Tonietto M, et al. Tau-PET imaging predicts cognitive decline and brain atrophy progression in early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2022;93:459-67.

213. Barthélemy NR, Saef B, Li Y, et al. CSF tau phosphorylation occupancies at T217 and T205 represent improved biomarkers of amyloid and tau pathology in Alzheimer’s disease. Nat Aging 2023;3:391-401.

214. Horie K, Salvadó G, Barthélemy NR, et al. CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease. Nat Med 2023;29:1954-63.

215. Silva MC, Ferguson FM, Cai Q, et al. Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models. Elife 2019;8:e45457.

Ageing and Neurodegenerative Diseases
ISSN 2769-5301 (Online)

Portico

All published articles will be preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles will be preserved here permanently:

https://www.portico.org/publishers/oae/