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Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression

Meftah, Soraya, Gan, Jian·2023·Frontiers in Synaptic Neuroscience
DOI 10.3389/fnsyn.2023.1129036PMC PMC10033629
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Abstract

The synapse has consistently been considered a vulnerable and critical target within Alzheimer’s disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer’s disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer’s disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer’s disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer’s disease, and what we know from Alzheimer’s disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer’s disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer’s disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer’s disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer’s disease. The synapse will certainly continue to be an important target within Alzheimer’s disease for the foreseeable future.

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  • In Alzheimer's disease, beta-amyloid (Aβ) accumulates within synapses, impairing neurotransmitter release, receptor signalling, and dendritic spine stability, strongly implicating Aβ in synaptic pathology.

    “In AD, beta-amyloid (Aβ) accumulates within synapses, impairing neurotransmitter release, receptor signalling, and dendritic spine stability, strongly implicating Aβ in synaptic pathology [7, 28].”

    From Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer’s disease mouse model (2025) · cites this paper as [28]

    Section 4 reports that Aβ affects NMDA receptors and synaptic vesicle dynamics, and that dendritic spines are lost near amyloid plaques in mouse models. It does not establish that Aβ accumulates within synapses in people with Alzheimer’s disease; its location-specific evidence concerns plaques near synapses, not Aβ within them. (LLM, conf=0.87)

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Research works printed but not linked: 248

  1. Abuhassan, 2014, Compensating for synaptic loss in Alzheimer’s disease., J. Comput. Neurosci., 36, 19, 10.1007/s10827-013-0462-8 · DOI
  2. Adaikkan, 2020, Gamma entrainment: Impact on neurocircuits, glia, and therapeutic opportunities., Trends Neurosci., 43, 24, 10.1016/j.tins.2019.11.001 · DOI
  3. Adams, 1987, Plasticity of the synaptic contact zone following loss of synapses in the cerebral cortex of aging humans., Brain Res., 424, 343, 10.1016/0006-8993(87)91479-x · DOI
  4. Adler, 2003, EEG coherence in Alzheimer’s dementia., J. Neural Transm., 110, 1051, 10.1007/s00702-003-0024-8 · DOI
  5. Ahmed, 2014, A novel in vivo model of tau propagation with rapid and progressive neurofibrillary tangle pathology: The pattern of spread is determined by connectivity, not proximity., Acta Neuropathol., 127, 667, 10.1007/s00401-014-1254-6 · DOI
  6. Algamal, 2022, Reduced excitatory neuron activity and interneuron-type-specific deficits in a mouse model of Alzheimer’s disease., Commun. Biol., 5, 10.1038/s42003-022-04268-x · DOI · Paper page
  7. 1911, Über eigenartige Krankheitsfälle des späteren Alters., Zeitsch. Neurol. Psychiatr., 4
  8. 2020, 2020 Alzheimer’s disease facts and figures., Alzheimers Dement., 16, 391, 10.1002/alz.12068 · DOI · Paper page
  9. Ambrad Giovannetti, 2019, Unsupervised excitation: GABAergic dysfunctions in Alzheimer’s disease., Brain Res., 1707, 216, 10.1016/j.brainres.2018.11.042 · DOI
  10. Araque, 1999, Tripartite synapses: Glia, the unacknowledged partner., Trends Neurosci., 22, 208, 10.1016/s0166-2236(98)01349-6 · DOI · Paper page
  11. Arias, 1995, beta-Amyloid peptide fragment 25-35 potentiates the calcium-dependent release of excitatory amino acids from depolarized hippocampal slices., J. Neurosci. Res., 41, 561, 10.1002/jnr.490410416 · DOI
  12. Arroyo-García, 2021, Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease., Mol. Psychiatry, 26, 5557, 10.1038/s41380-021-01257-0 · DOI
  13. Athar, 2021, Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease., Mol. Biol. Rep., 48, 5629, 10.1007/s11033-021-06512-9 · DOI
  14. Baazaoui, 2017, Synaptic compensation as a probable cause of prolonged mild cognitive impairment in Alzheimer’s Disease: Implications from a transgenic mouse model of the disease., J. Alzheimers Dis., 56, 1385, 10.3233/JAD-160845 · DOI
  15. Bagattini, 2019, Predicting Alzheimer’s disease severity by means of TMS-EEG coregistration., Neurobiol. Aging, 80, 38, 10.1016/j.neurobiolaging.2019.04.008 · DOI
  16. Barbier, 2019, Role of tau as a microtubule-associated protein: Structural and functional aspects., Front. Aging Neurosci., 11, 10.3389/fnagi.2019.00204 · DOI
  17. Bartzokis, 2011, Alzheimer’s disease as homeostatic responses to age-related myelin breakdown., Neurobiol. Aging, 32, 1341, 10.1016/j.neurobiolaging.2009.08.007 · DOI · Paper page
  18. Beckman, 2019, Oligomeric Aβ in the monkey brain impacts synaptic integrity and induces accelerated cortical aging., Proc Natl Acad Sci U S A., 116, 26239, 10.1073/pnas.1902301116 · DOI · Paper page
  19. Bejanin, 2017, Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease., Brain, 140, 3286, 10.1093/brain/awx243 · DOI · Paper page
  20. Benitez, 2021, Knock-in models related to Alzheimer’s disease: Synaptic transmission, plaques and the role of microglia., Mol. Neurodegener., 16, 1, 10.1186/s13024-021-00457-0 · DOI
  21. Bertoni-Freddari, 1988, Quantitative morphology of synaptic plasticity in the aging brain., Scanning Microsc., 2, 1027
  22. Bi, 2002, N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer’s disease., J. Neurol. Sci., 200, 11, 10.1016/s0022-510x(02)00087-4 · DOI
  23. Black, 1996, Tau is enriched on dynamic microtubules in the distal region of growing axons., J. Neurosci., 16, 3601, 10.1523/JNEUROSCI.16-11-03601.1996 · DOI · Paper page
  24. Bliss, 1993, A synaptic model of memory: Long-term potentiation in the hippocampus., Nature, 361, 31, 10.1038/361031a0 · DOI · Paper page
  25. Bliss, 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path., J. Physiol., 232, 331, 10.1113/jphysiol.1973.sp010273 · DOI · Paper page
  26. Booth, 2014, Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1., Eur. J. Neurosci., 39, 1074, 10.1111/ejn.12549 · DOI
  27. Booth, 2016, Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy., J. Neurosci., 36, 350, 10.1523/JNEUROSCI.2151-15.2016 · DOI
  28. Brady, 2022, Alterations to parvalbumin-expressing interneuron function and associated network oscillations in the hippocampal – medial prefrontal cortex circuit during natural sleep in APPNL-G-F mice., bioRxiv, 10.1101/2022.02.08.479119 · DOI
  29. Brown, 2011, Altered intrinsic neuronal excitability and reduced Na+ currents in a mouse model of Alzheimer’s disease., Neurobiol. Aging, 32, 2109.e1, 10.1016/j.neurobiolaging.2011.05.025 · DOI
  30. Busche, 2019, Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo., Nat. Neurosci., 22, 57, 10.s1038/s41593-018-0289-8
  31. Busse, 2013, Automated analysis of a diverse synapse population., PLoS Comput. Biol., 9, 10.1371/journal.pcbi.1002976 · DOI
  32. Butt, 2019, Oligodendroglial Cells in Alzheimer’s Disease., Adv. Exp. Med. Biol., 1175, 325, 10.1007/978-981-13-9913-8_12 · DOI
  33. Buzsaki, 2006, Rhythms of the Brain., 10.1093/acprof:oso/9780195301069.001.0001 · DOI · Paper page
  34. Byun, 2018, A novel in vitro live-imaging assay of astrocyte-mediated phagocytosis using pH indicator-conjugated synaptosomes., J. Vis. Exp., 132, 10.3791/56647 · DOI
  35. Caccavano, 2020, Inhibitory Parvalbumin Basket Cell Activity is Selectively Reduced during Hippocampal Sharp Wave Ripples in a Mouse Model of Familial Alzheimer’s Disease., J. Neurosci., 40, 5116, 10.1523/JNEUROSCI.0425-20.2020 · DOI
  36. Calvo-Flores Guzmán, 2018, The GABAergic system as a therapeutic target for Alzheimer’s disease., J. Neurochem., 146, 649, 10.1111/jnc.14345 · DOI
  37. Casillas-Espinosa, 2012, Regulators of synaptic transmission: Roles in the pathogenesis and treatment of epilepsy., Epilepsia, 53, 41, 10.1111/epi.12034 · DOI
  38. Casula, 2023, Regional Precuneus Cortical Hyperexcitability in Alzheimer’s Disease Patients., Ann. Neurol., 93, 371, 10.1002/ana.26514 · DOI
  39. Chan, Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer’s disease., J. Intern. Med., 290, 993, 10.1111/joim.13329 · DOI
  40. Chan, Gamma Frequency Sensory Stimulation in Probable Mild Alzheimer’s Dementia Patients: Results of a Preliminary Clinical Trial., medRxiv, 10.1101/2021.03.01.21252717 · DOI
  41. Chartier-Harlin, 1991, Early-onset Alzheimer’s disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene., Nature, 353, 844, 10.1038/353844a0 · DOI · Paper page
  42. Chen, 2018, Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging., JAMA Neurol., 75, 1215, 10.1001/jamaneurol.2018.1836 · DOI · Paper page
  43. Chung, 2020, Dissociation of somatostatin and parvalbumin interneurons circuit dysfunctions underlying hippocampal theta and gamma oscillations impaired by amyloid β oligomers in vivo., Brain Struct. Funct., 225, 935, 10.1007/s00429-020-02044-3 · DOI
  44. Cimenser, 2021, Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer’s Disease Patients., Front. Syst. Neurosci., 15, 10.3389/fnsys.2021.746859 · DOI
  45. Colom-Cadena, 2020, The clinical promise of biomarkers of synapse damage or loss in Alzheimer’s disease., Alzheimers Res. Therapy, 12, 1, 10.1186/S13195-020-00588-4 · DOI · Paper page
  46. Corder, 1993, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families., Science, 261, 921, 10.1126/science.8346443 · DOI · Paper page
  47. Crimins, 2013, The intersection of amyloid β and tau in glutamatergic synaptic dysfunction and collapse in Alzheimer’s disease., Ageing Res. Rev., 12, 757, 10.1016/j.arr.2013.03.002 · DOI
  48. Crimins, 2012, Electrophysiological changes precede morphological changes to frontal cortical pyramidal neurons in the rTg4510 mouse model of progressive tauopathy., Acta Neuropathol., 124, 777, 10.1007/s00401-012-1038-9 · DOI
  49. Crimins, 2011, Homeostatic responses by surviving cortical pyramidal cells in neurodegenerative tauopathy., Acta Neuropathol., 122, 551, 10.1007/s00401-011-0877-0 · DOI
  50. Dalby, 2014, Altered function of hippocampal CA1 pyramidal neurons in the rTg4510 mouse model of tauopathy., J. Alzheimers Dis., 40, 429, 10.3233/JAD-131358 · DOI
  51. Damoiseaux, 2012, Functional connectivity tracks clinical deterioration in Alzheimer’s disease., Neurobiol. Aging, 33, 828.e19, 10.1016/j.neurobiolaging.2011.06.024 · DOI
  52. Decker, 2015, Pro-aggregant Tau impairs mossy fiber plasticity due to structural changes and Ca(++) dysregulation., Acta Neuropathol. Commun., 3, 10.1186/s40478-015-0193-3 · DOI
  53. DeKosky, 1990, Synapse loss in frontal cortex biopsies in Alzheimer’s disease: Correlation with cognitive severity., Ann. Neurol., 27, 457, 10.1002/ana.410270502 · DOI · Paper page
  54. DeKosky, 1996, Structural correlates of cognition in dementia: Quantification and assessment of synapse change., Neurodegeneration, 5, 417, 10.1006/neur.1996.0056 · DOI · Paper page
  55. Desai, 2009, Triple-transgenic Alzheimer’s disease mice exhibit region-specific abnormalities in brain myelination patterns prior to appearance of amyloid and tau pathology., Glia, 57, 54, 10.1002/glia.20734 · DOI · Paper page
  56. Dickerson, 2005, Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD., Neurology, 65, 404, 10.1212/01.wnl.0000171450.97464.49 · DOI · Paper page
  57. Domínguez-Álvaro, 2019, 3D Electron Microscopy Study of Synaptic Organization of the Normal Human Transentorhinal Cortex and Its Possible Alterations in Alzheimer’s Disease., eNeuro, 6, ENEURO.0140, 10.1523/ENEURO.0140-19.2019 · DOI
  58. Dong, 2007, Spatial relationship between synapse loss and beta-amyloid deposition in Tg2576 mice., J. Comp. Neurol., 500, 311, 10.1002/cne.21176 · DOI
  59. Du, 2019, Small changes in synaptic gain lead to seizure-like activity in neuronal network at criticality., Sci. Rep., 9, 10.1038/s41598-018-37646-9 · DOI
  60. Düzel, 2010, Brain oscillations and memory., Curr. Opin. Neurobiol., 20, 143, 10.1016/j.conb.2010.01.004 · DOI
  61. Eckermann, 2007, The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy., J. Biol. Chem., 282, 31755, 10.1074/jbc.M705282200 · DOI · Paper page
  62. Engert, 1999, Dendritic spine changes associated with hippocampal long-term synaptic plasticity., Nature, 399, 66, 10.1038/19978 · DOI · Paper page
  63. Etter, 2019, Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model., Nat. Commun., 10, 10.1038/s41467-019-13260-9 · DOI
  64. Fá, 2016, Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory., Sci. Rep., 6, 10.1038/srep19393 · DOI
  65. Fell, 2011, The role of phase synchronization in memory processes., Nat. Rev. Neurosci., 12, 105, 10.1038/nrn2979 · DOI · Paper page
  66. Forner, 2017, Synaptic Impairment in Alzheimer’s Disease: A Dysregulated Symphony., Trends Neurosci., 40, 347, 10.1016/j.tins.2017.04.002 · DOI · Paper page
  67. Frere, 2018, Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse., Neuron, 97, 32, 10.1016/j.neuron.2017.11.028 · DOI
  68. Funane, 2022, Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer’s disease., Front. Syst. Neurosci., 16, 10.3389/fnsys.2022.955178 · DOI
  69. Gamblin, 2003, Caspase cleavage of tau: Linking amyloid and neurofibrillary tangles in Alzheimer’s disease., Proc. Natl. Acad. Sci. U.S.A., 100, 10032, 10.1073/pnas.1630428100 · DOI · Paper page
  70. Gan, 2017, Phase-Locked Inhibition, but Not Excitation. Underlies Hippocampal Ripple Oscillations in Awake Mice In Vivo., Neuron, 93, 308, 10.1016/j.neuron.2016.12.018 · DOI
  71. Gelman, 2018, Differences in Synaptic Dysfunction Between rTg4510 and APP/PS1 Mouse Models of Alzheimer’s Disease., J. Alzheimers Dis., 61, 195, 10.3233/JAD-170457 · DOI
  72. Gengler, 2010, Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer’s disease is impaired in old but not young mice., PLoS One, 5, 10.1371/journal.pone.0009764 · DOI
  73. Giorgi, 2020, Epilepsy and Alzheimer’s Disease: Potential mechanisms for an association., Brain Res. Bull., 160, 107, 10.1016/j.brainresbull.2020.04.009 · DOI
  74. Giovannetti, 2018, Restoring memory by optogenetic synchronization of hippocampal oscillations in an Alzheimer’s disease mouse model., bioRxiv, 10.1101/363820 · DOI
  75. Goate, 2017, LTP and memory impairment caused by extracellular Ab and Tau oligomers is APP-dependent, Elife, 6, 10.7554/eLife.26991 · DOI · Paper page
  76. Gong, 2009, Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer’s disease., Brain Res., 1292, 191, 10.1016/j.brainres.2009.07.056 · DOI
  77. Goodman, 2018, Theta-Gamma coupling and working memory in Alzheimer’s dementia and mild cognitive impairment., Front. Aging Neurosci., 10, 10.3389/FNAGI.2018.00101/BIBTEX · DOI
  78. Govindpani, 2020, Impaired Expression of GABA Signaling Components in the Alzheimer’s Disease Middle Temporal Gyrus., Int. J. Mol. Sci., 21, 10.3390/ijms21228704 · DOI
  79. Green, 2019, Functional networks are impaired by elevated tau-protein but reversible in a regulatable Alzheimer’s disease mouse model., Mol. Neurodegener., 14, 10.1186/s13024-019-0316-6 · DOI
  80. Griner, 2019, Structure-based inhibitors of amyloid beta core suggest a common interface with tau., eLife, 8, 10.7554/eLife.46924 · DOI · Paper page
  81. Grosenick, 2015, Closed-loop and activity-guided optogenetic control., Neuron, 86, 106, 10.1016/j.neuron.2015.03.034 · DOI
  82. Hanson, 2020, GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer’s Disease Models., Cell Rep., 30, 381, 10.1016/j.celrep.2019.12.030 · DOI
  83. Hardy, A disorder of cortical GABAergic innervation in Alzheimer’s disease., Neurosci. Lett., 73, 192, 10.1016/0304-3940(87)90016-4 · DOI
  84. Hardy, Region-specific loss of glutamate innervation in Alzheimer’s disease., Neurosci. Lett., 73, 77, 10.1016/0304-3940(87)90034-6 · DOI
  85. Hardy, 1992, Alzheimer’s disease: The amyloid cascade hypothesis., Science, 256, 184, 10.1126/science.1566067 · DOI · Paper page
  86. Harris, 1995, beta-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: Implications for Alzheimer’s disease., Neuroreport, 6, 1875, 10.1097/00001756-199510020-00013 · DOI
  87. Hatanpää, 1999, Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease., J. Neuropathol. Exp. Neurol., 58, 637, 10.1097/00005072-199906000-00008 · DOI
  88. Hauptmann, 2006, Mitochondrial dysfunction in sporadic and genetic Alzheimer’s disease., Exp. Gerontol., 41, 668, 10.1016/j.exger.2006.03.012 · DOI
  89. Hebb, 1949, The organization of behavior: a neuropsychological theory.
  90. Hector, 2021, Hyperactivity Induced by Soluble Amyloid-β Oligomers in the Early Stages of Alzheimer’s Disease., Front. Mol. Neurosci., 13, 10.3389/fnmol.2020.600084 · DOI
  91. Henstridge, 2016, Synaptic pathology: A shared mechanism in neurological disease., Ageing Res. Rev., 28, 72, 10.1016/j.arr.2016.04.005 · DOI
  92. Herweg, 2020, Theta Oscillations in Human Memory., Trends Cogn. Sci., 24, 208, 10.1016/j.tics.2019.12.006 · DOI
  93. Hesse, 2019, Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype., Acta Neuropathol. Commun., 7, 10.1186/s40478-019-0847-7 · DOI · Paper page
  94. Hijazi, 2020, Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer’s disease., Mol. Psychiatry, 25, 3380, 10.1038/s41380-019-0483-4 · DOI · Paper page
  95. Hill, 2019, Introduction of Tau Oligomers into Cortical Neurons Alters Action Potential Dynamics and Disrupts Synaptic Transmission and Plasticity., eNeuro, 6, ENEURO.0166, 10.1523/ENEURO.0166-19.2019 · DOI
  96. Hoffmann, 2013, Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice., Acta Neuropathol. Commun., 1, 10.1186/2051-5960-1-82 · DOI
  97. Hollnagel, 2019, Early alterations in hippocampal perisomatic GABAergic synapses and network oscillations in a mouse model of Alzheimer’s disease amyloidosis., PLoS One, 14, 10.1371/journal.pone.0209228 · DOI
  98. Hoover, 2010, Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration., Neuron, 68, 1067, 10.1016/j.neuron.2010.11.030 · DOI · Paper page
  99. Huang, 2004, Apolipoprotein E: Diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer’s disease., J. Mol. Neurosci., 23, 189, 10.1385/JMN:23:3:189 · DOI · Paper page
  100. Hulshof, 2022, The Role of Astrocytes in Synapse Loss in Alzheimer’s Disease: A Systematic Review., Front. Cell Neurosci., 16, 10.3389/fncel.2022.899251 · DOI
  101. Irizarry, 2012, Incidence of new-onset seizures in mild to moderate Alzheimer disease., Arch. Neurol., 69, 368, 10.1001/archneurol.2011.830 · DOI
  102. Isla, 2021, Efficacy of preclinical pharmacological interventions against alterations of neuronal network oscillations in Alzheimer’s disease: A systematic review., Exp. Neurol., 343, 10.1016/j.expneurol.2021.113743 · DOI
  103. Ittner, 2010, Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models., Cell, 142, 387, 10.1016/j.cell.2010.06.036 · DOI · Paper page
  104. Jack, 2009, Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: Implications for sequence of pathological events in Alzheimer’s disease., Brain, 132, 1355, 10.1093/brain/awp062 · DOI · Paper page
  105. Jackson, 2017, Altered Synapse Stability in the Early Stages of Tauopathy., Cell Rep., 18, 3063, 10.1016/j.celrep.2017.03.013 · DOI
  106. Jackson, 2020, Differential aberrant structural synaptic plasticity in axons and dendrites ahead of their degeneration in tauopathy., bioRxiv, 10.1101/2020.04.29.067629 · DOI
  107. Jadhav, 2015, Tau-mediated synaptic damage in Alzheimer’s disease., Transl. Neurosci., 6, 214, 10.1515/tnsci-2015-0023 · DOI
  108. Jantaratnotai, 2003, Amyloid beta peptide-induced corpus callosum damage and glial activation in vivo., Neuroreport, 14, 1429, 10.1097/00001756-200308060-00005 · DOI
  109. Ju, 2022, Pathological mechanisms and therapeutic strategies for Alzheimer’s disease., Neural Regen. Res., 17, 543, 10.4103/1673-5374.320970 · DOI
  110. Kawabata, 2022, Excessive/Aberrant and maladaptive synaptic plasticity: A hypothesis for the pathogenesis of Alzheimer’s Disease., Front. Aging Neurosci., 14, 10.3389/fnagi.2022.913693 · DOI · Paper page
  111. Kerrigan, 2014, Characterization of altered intrinsic excitability in hippocampal CA1 pyramidal cells of the Aβ-overproducing PDAPP mouse., Neuropharmacology, 79, 515, 10.1016/j.neuropharm.2013.09.004 · DOI
  112. Kitchigina, 2018, Alterations of Coherent Theta and Gamma Network Oscillations as an Early Biomarker of Temporal Lobe Epilepsy and Alzheimer’s Disease., Front. Integr. Neurosci., 12, 10.3389/fnint.2018.00036 · DOI
  113. Konorski, 1948, Conditioned reflexes and neuron organization.
  114. Kopeikina, 2011, Tau accumulation causes mitochondrial distribution deficits in neurons in a mouse model of tauopathy and in human Alzheimer’s disease brain., Am. J. Pathol., 179, 2071, 10.1016/j.ajpath.2011.07.004 · DOI
  115. Kopeikina, 2012, Soluble forms of tau are toxic in Alzheimer’s disease., Transl. Neurosci., 3, 223, 10.2478/s13380-012-0032-y · DOI · Paper page
  116. Kovacs, 2015, Invited review: Neuropathology of tauopathies: Principles and practice., Neuropathol. Appl. Neurobiol., 41, 3, 10.1111/nan.12208 · DOI · Paper page
  117. Kuchibhotla, 2014, Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo., Proc. Natl. Acad. Sci. U.S.A., 111, 510, 10.1073/pnas.1318807111 · DOI · Paper page
  118. Kurucu, 2022, Inhibitory synapse loss and accumulation of amyloid beta in inhibitory presynaptic terminals in Alzheimer’s disease., Eur. J. Neurol., 29, 1311, 10.1111/ene.15043 · DOI
  119. Landau, 2011, Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI., Neurobiol. Aging, 32, 1207, 10.1016/j.neurobiolaging.2009.07.002 · DOI · Paper page
  120. Latif-Hernandez, 2020, The two faces of synaptic failure in AppNL-G-F knock-in mice., Alzheimers Res. Ther., 12, 10.1186/s13195-020-00667-6 · DOI
  121. Lauterborn, 2021, Increased excitatory to inhibitory synaptic ratio in parietal cortex samples from individuals with Alzheimer’s disease., Nat. Commun., 12, 10.1038/s41467-021-22742-8 · DOI
  122. Laxton, 2010, A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease., Ann. Neurol., 68, 521, 10.1002/ana.22089 · DOI
  123. Lepeta, 2016, Synaptopathies: Synaptic dysfunction in neurological disorders – A review from students to students., J. Neurochem., 138, 785, 10.1111/JNC.13713 · DOI · Paper page
  124. Li, 2003, Huntington’s disease: A synaptopathy?, Trends Mol. Med., 9, 414, 10.1016/j.molmed.2003.08.006 · DOI
  125. Li, 2020, A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer’s brain., J. Neurochem., 154, 583, 10.1111/jnc.15007 · DOI · Paper page
  126. Liu, 2019, Regulation of Neurotransmitter Release by Amyloid Precursor Protein Through Synapsin Phosphorylation., Neurochem. Res., 44, 683, 10.1007/s11064-017-2418-2 · DOI
  127. Liu, 2019, The Role of NMDA Receptors in Alzheimer’s Disease., Front. Neurosci., 13, 10.3389/fnins.2019.00043 · DOI · Paper page
  128. LoPresti, 1995, Functional implications for the microtubule-associated protein tau: Localization in oligodendrocytes., Proc. Natl. Acad. Sci. U.S.A., 92, 10369, 10.1073/pnas.92.22.10369 · DOI · Paper page
  129. Marcello, 2012, SAP97-mediated local trafficking is altered in Alzheimer disease patients’ hippocampus., Neurobiol. Aging, 33, 422.e1, 10.1016/j.neurobiolaging.2010.09.015 · DOI
  130. Marchetti, 2011, Hippocampal synaptic plasticity in Alzheimer’s disease: What have we learned so far from transgenic models?, Rev. Neurosci., 22, 373, 10.1515/RNS.2011.035 · DOI
  131. Marinković, 2019, In vivo imaging reveals reduced activity of neuronal circuits in a mouse tauopathy model., Brain, 142, 1051, 10.1093/brain/awz035 · DOI
  132. Marsh, 2018, Synaptic dysfunction in Alzheimer’s disease: The effects of amyloid beta on synaptic vesicle dynamics as a novel target for therapeutic intervention., Neural Regen. Res., 13, 616, 10.4103/1673-5374.230276 · DOI
  133. Marsh, 2017, Synapsin I phosphorylation is dysregulated by beta-amyloid oligomers and restored by valproic acid., Neurobiol. Dis., 106, 63, 10.1016/j.nbd.2017.06.011 · DOI
  134. Martinez-Losa, 2018, Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer’s Disease., Neuron, 98, 75, 10.1016/j.neuron.2018.02.029 · DOI
  135. Martínez-Serra, 2022, Emerging insights into synapse dysregulation in Alzheimer’s disease., Brain Commun., 4, 10.1093/braincomms/fcac083 · DOI
  136. Mckean, 2021, A Review of the Current Mammalian Models of Alzheimer’s Disease and Challenges That Need to Be Overcome., Int. J. Mol. Sci., 22, 10.3390/ijms222313168 · DOI
  137. Mehak, 2022, Theta and gamma oscillatory dynamics in mouse models of Alzheimer’s disease: A path to prospective therapeutic intervention., Neurosci. Biobehav. Rev., 136, 10.1016/j.neubiorev.2022.104628 · DOI
  138. Micu, 2006, NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia., Nature, 439, 988, 10.1038/nature04474 · DOI
  139. Mirzayi, 2022, Optogenetics: Implications for Alzheimer’s disease research and therapy., Mol. Brain, 15, 10.1186/s13041-022-00905-y · DOI
  140. Miyamoto, 2017, Phosphorylation of tau at Y18, but not tau-fyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture., Mol. Neurodegener., 12, 10.1186/s13024-017-0176-x · DOI
  141. Mondragón-Rodríguez, 2012, Interaction of endogenous tau protein with synaptic proteins is regulated by N-methyl-D-aspartate receptor-dependent tau phosphorylation., J. Biol. Chem., 287, 32040, 10.1074/jbc.M112.401240 · DOI · Paper page
  142. Montero-Crespo, 2021, Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease., Brain, 144, 553, 10.1093/brain/awaa406 · DOI
  143. Moreno, 2011, Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA., Front. Synaptic Neurosci., 3, 10.3389/fnsyn.2011.00003 · DOI
  144. Moreno, 2016, Tau pathology-mediated presynaptic dysfunction., Neuroscience, 325, 30, 10.1016/j.neuroscience.2016.03.044 · DOI
  145. Moretti, 2010, EEG markers discriminate among different subgroup of patients with mild cognitive impairment., Am. J. Alzheimers Dis. Other Demen., 25, 58, 10.1177/1533317508329814 · DOI
  146. Mota, 2014, Dysfunctional synapse in Alzheimer’s disease - A focus on NMDA receptors., Neuropharmacology, 76, 16, 10.1016/j.neuropharm.2013.08.013 · DOI
  147. Mucke, 2000, High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation., J. Neurosci., 20, 4050, 10.1523/JNEUROSCI.20-11-04050.2000 · DOI · Paper page
  148. Mulder, 2011, Molecular reorganization of endocannabinoid signalling in Alzheimer’s disease., Brain, 134, 1041, 10.1093/brain/awr046 · DOI
  149. Nardone, 2021, TMS-EEG Co-Registration in Patients with Mild Cognitive Impairment. Alzheimer’s Disease and Other Dementias: A Systematic Review., Brain Sci., 11, 10.3390/brainsci11030303 · DOI
  150. Neuman, 2015, Evidence for Alzheimer’s disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons., Brain Struct. Funct., 220, 3143, 10.1007/s00429-014-0848-z · DOI
  151. Nguyen, 2021, Advances in developing therapeutic strategies for Alzheimer’s disease., Biomed. Pharmacother., 139, 10.1016/j.biopha.2021.111623 · DOI
  152. Nicastro, 2016, From here to epilepsy: The risk of seizure in patients with Alzheimer’s disease., Epileptic Disord., 18, 1, 10.1684/epd.2016.0808 · DOI
  153. Nicole, 2016, Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation., Sci. Rep., 6, 10.1038/srep22728 · DOI
  154. Nordberg, 1986, Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains., Neurosci. Lett., 72, 115, 10.1016/0304-3940(86)90629-4 · DOI
  155. O’Brien, 2010, Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline., Neurology, 74, 1969, 10.1212/WNL.0b013e3181e3966e · DOI
  156. Ohline, 2022, Altered membrane properties but unchanged intrinsic excitability and spontaneous postsynaptic currents in an aged APP swe/PS1dE9 model of Alzheimer’s disease., Front. Cell Neurosci., 16, 10.3389/fncel.2022.958876 · DOI
  157. Orr, 2017, Brief overview of Tauopathy: Causes, consequences, and therapeutic strategies., Trends Pharmacol Sci., 38, 637, 10.1016/j.tips.2017.03.011 · DOI
  158. Oyelami, 2016, Age-dependent concomitant changes in synaptic dysfunction and GABAergic pathway in the APP/PS1 mouse model., Acta Neurobiol. Exp., 76, 282, 10.21307/ane-2017-027 · DOI
  159. Palop, 2007, Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease., Neuron, 55, 697, 10.1016/j.neuron.2007.07.025 · DOI · Paper page
  160. Palop, 2016, Network abnormalities and interneuron dysfunction in Alzheimer disease., Nat. Rev. Neurosci., 17, 777, 10.1038/nrn.2016.141 · DOI · Paper page
  161. Papanikolaou, 2022, Plasticity in visual cortex is disrupted in a mouse model of tauopathy., Commun. Biol., 5, 10.1038/s42003-022-03012-9 · DOI
  162. Park, 2020, Optogenetic activation of parvalbumin and somatostatin interneurons selectively restores theta-nested gamma oscillations and oscillation-induced spike timing-dependent long-term potentiation impaired by amyloid β oligomers., BMC Biol., 18, 10.1186/s12915-019-0732-7 · DOI
  163. Perea, 2009, Tripartite synapses: Astrocytes process and control synaptic information., Trends Neurosci., 32, 421, 10.1016/j.tins.2009.05.001 · DOI · Paper page
  164. Pereira, 2021, Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease., Brain, 144, 310, 10.1093/brain/awaa395 · DOI
  165. Perry, 1987, Nicotinic receptor abnormalities in Alzheimer’s and Parkinson’s diseases., J. Neurol. Neurosurg. Psychiatry, 50, 806, 10.1136/jnnp.50.6.806 · DOI
  166. Petrache, 2019, Aberrant Excitatory-Inhibitory Synaptic Mechanisms in Entorhinal Cortex Microcircuits During the Pathogenesis of Alzheimer’s Disease., Cereb. Cortex, 29, 1834, 10.1093/cercor/bhz016 · DOI · Paper page
  167. Phongpreecha, 2021, Single-synapse analyses of Alzheimer’s disease implicate pathologic tau. DJ1, CD47, and ApoE., Sci. Adv., 7, 10.1126/sciadv.abk0473 · DOI
  168. Piccioni, 2021, Targeting Microglia-Synapse Interactions in Alzheimer’s Disease., Int. J. Mol. Sci., 22, 10.3390/ijms22052342 · DOI
  169. Pickett, 2019, Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer’s Disease., Cell Rep., 29, 3592, 10.1016/j.celrep.2019.11.044 · DOI · Paper page
  170. Polanco, 2018, Amyloid-β and tau complexity - towards improved biomarkers and targeted therapies., Nat. Rev. Neurol., 14, 22, 10.1038/nrneurol.2017.162 · DOI
  171. Polydoro, 2014, Soluble pathological tau in the entorhinal cortex leads to presynaptic deficits in an early Alzheimer’s disease model., Acta Neuropathol., 127, 257, 10.1007/s00401-013-1215-5 · DOI · Paper page
  172. Pooler, 2013, Physiological release of endogenous tau is stimulated by neuronal activity., EMBO Rep., 14, 389, 10.1038/embor.2013.15 · DOI · Paper page
  173. Poorkaj, 1998, Tau is a candidate gene for chromosome 17 frontotemporal dementia., Ann. Neurol., 43, 815, 10.1002/ana.410430617 · DOI · Paper page
  174. Prince, 2015, World Alzheimer report 2015: The global impact of dementia: An analysis of prevalence, incidence, cost and trends
  175. Prince, 2021, Alzheimer’s pathology causes impaired inhibitory connections and reactivation of spatial codes during spatial navigation., Cell Rep., 35, 10.1016/j.celrep.2021.109008 · DOI
  176. Puzzo, 2020, Tau is not necessary for amyloid-β-induced synaptic and memory impairments., J. Clin. Invest., 130, 4831, 10.1172/JCI137040 · DOI
  177. Rajendran, 2018, Microglia-Mediated Synapse Loss in Alzheimer’s Disease., J. Neurosci., 38, 2911, 10.1523/JNEUROSCI.1136-17.2017 · DOI · Paper page
  178. Reddy, 2005, Differential loss of synaptic proteins in Alzheimer’s disease: Implications for synaptic dysfunction., J. Alzheimers Dis., 7, 103, 10.3233/jad-2005-7203 · DOI
  179. Rhein, 2009, Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice., Proc. Natl. Acad. Sci. U.S.A., 106, 20057, 10.1073/pnas.0905529106 · DOI · Paper page
  180. Ridler, 2020, Impaired speed encoding and grid cell periodicity in a mouse model of tauopathy., eLife, 9, 10.7554/eLife.59045 · DOI
  181. Roberson, 2011, Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease., J. Neurosci., 31, 700, 10.1523/JNEUROSCI.4152-10.2011 · DOI · Paper page
  182. Roberson, 2007, Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model., Science, 316, 750, 10.1126/science.1141736 · DOI · Paper page
  183. Romanelli, 1990, Advanced Alzheimer’s disease is a risk factor for late-onset seizures., Arch. Neurol., 47, 847, 10.1001/archneur.1990.00530080029006 · DOI
  184. Russell, 2012, Amyloid-β acts as a regulator of neurotransmitter release disrupting the interaction between synaptophysin and VAMP2., PLoS One, 7, 10.1371/journal.pone.0043201 · DOI
  185. Rylett, 1983, Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer’s disease., Brain Res., 289, 169, 10.1016/0006-8993(83)90017-3 · DOI
  186. Sahara, 2014, Biochemical Distribution of Tau Protein in Synaptosomal Fraction of Transgenic Mice Expressing Human P301L Tau., Front. Neurol., 5, 10.3389/fneur.2014.00026 · DOI
  187. Salter, 2005, NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury., Nature, 438, 1167, 10.1038/nature04301 · DOI
  188. Santacruz, 2005, Tau suppression in a neurodegenerative mouse model improves memory function., Science, 309, 476, 10.1126/science.1113694 · DOI · Paper page
  189. Saunders, 1993, Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease., Neurology, 43, 1467, 10.1212/wnl.43.8.1467 · DOI · Paper page
  190. Scaduto, 2023, Functional excitatory to inhibitory synaptic imbalance and loss of cognitive performance in people with Alzheimer’s disease neuropathologic change., Acta Neuropathol., 145, 303, 10.1007/s00401-022-02526-0 · DOI
  191. Schaler, 2021, PAC1 receptor-mediated clearance of tau in postsynaptic compartments attenuates tau pathology in mouse brain., Sci. Transl. Med., 13, 10.1126/scitranslmed.aba7394 · DOI
  192. Scheff, 2003, Synaptic pathology in Alzheimer’s disease: A review of ultrastructural studies., Neurobiol. Aging, 24, 1029, 10.1016/j.neurobiolaging.2003.08.002 · DOI · Paper page
  193. Scheff, 2007, Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment., Neurology, 68, 1501, 10.1212/01.wnl.0000260698.46517.8f · DOI · Paper page
  194. Scheff, 2006, Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment., Neurobiol. Aging, 27, 1372, 10.1016/j.neurobiolaging.2005.09.012 · DOI · Paper page
  195. Schirinzi, 2020, The continuum between neurodegeneration, brain plasticity, and movement: A critical appraisal., Rev. Neurosci., 31, 723, 10.1515/revneuro-2020-0011 · DOI
  196. Schmid, 2016, Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer’s Disease Model., Neuron, 92, 114, 10.1016/j.neuron.2016.08.034 · DOI
  197. Schnitzler, 2005, Normal and pathological oscillatory communication in the brain., Nat. Rev. Neurosci., 6, 285, 10.1038/nrn1650 · DOI
  198. Selkoe, 1991, The molecular pathology of Alzheimer’s disease., Neuron, 6, 487, 10.1016/0896-6273(91)90052-2 · DOI · Paper page
  199. Senova, 2018, Fornical Closed-Loop Stimulation for Alzheimer’s Disease., Trends Neurosci., 41, 418, 10.1016/j.tins.2018.03.015 · DOI
  200. Shipton, 2011, Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation., J. Neurosci., 31, 1688, 10.1523/JNEUROSCI.2610-10.2011 · DOI · Paper page

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Metadata

Authors
Meftah, S., & Gan, J.
Venue
Frontiers in Synaptic Neuroscience
Publisher
Frontiers Media SA
Published
2023-03-09
Volume
15
ISSN
1663-3563
DOI
10.3389/fnsyn.2023.1129036
PMC
PMC10033629
Cited by
205
References
42
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
UK Dementia Research Institute

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