1932

Abstract

A major mystery of many types of neurological and psychiatric disorders, such as Alzheimer's disease (AD), remains the underlying, disease-specific neuronal damage. Because of the strong interconnectivity of neurons in the brain, neuronal dysfunction necessarily disrupts neuronal circuits. In this article, we review evidence for the disruption of large-scale networks from imaging studies of humans and relate it to studies of cellular dysfunction in mouse models of AD. The emerging picture is that some forms of early network dysfunctions can be explained by excessively increased levels of neuronal activity. The notion of such neuronal hyperactivity receives strong support from in vivo and in vitro cellular imaging and electrophysiological recordings in the mouse, which provide mechanistic insights underlying the change in neuronal excitability. Overall, some key aspects of AD-related neuronal dysfunctions in humans and mice are strikingly similar and support the continuation of such a translational strategy.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-080317-061725
2018-07-08
2024-04-24
Loading full text...

Full text loading...

/deliver/fulltext/neuro/41/1/annurev-neuro-080317-061725.html?itemId=/content/journals/10.1146/annurev-neuro-080317-061725&mimeType=html&fmt=ahah

Literature Cited

  1. Allen G, Barnard H, McColl R, Hester AL, Fields JA et al. 2007. Reduced hippocampal functional connectivity in Alzheimer disease. Arch. Neurol. 64:1482–87
    [Google Scholar]
  2. Alzheimer A 1907. Über eine eigenartige Erkrankung der Hirnrinde. Allg. Z. Psychiatr. Phys.-Gerichtl. Med. 64:146–48
    [Google Scholar]
  3. Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR 1995. An English translation of Alzheimer's 1907 paper, “Über eine eigenartige Erkankung der Hirnrinde. Clin. Anat. 8:429–31
    [Google Scholar]
  4. Arbel-Ornath M, Hudry E, Boivin JR, Hashimoto T, Takeda S et al. 2017. Soluble oligomeric amyloid-β induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain. Mol. Neurodegener. 12:27
    [Google Scholar]
  5. Bai F, Watson DR, Shi Y, Wang Y, Yue C et al. 2011. Specifically progressive deficits of brain functional marker in amnestic type mild cognitive impairment. PLOS ONE 6:e24271
    [Google Scholar]
  6. Bakker A, Albert MS, Krauss G, Speck CL, Gallagher M 2015. Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance. NeuroImage Clin 7:688–98
    [Google Scholar]
  7. Bakker A, Krauss GL, Albert MS, Speck CL, Jones LR et al. 2012. Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74:467–74
    [Google Scholar]
  8. Barry AE, Klyubin I, Mc Donald JM, Mably AJ, Farrell MA et al. 2011. Alzheimer's disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J. Neurosci. 31:7259–63
    [Google Scholar]
  9. Bero AW, Yan P, Roh JH, Cirrito JR, Stewart FR et al. 2011. Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat. Neurosci. 14:750–56
    [Google Scholar]
  10. Bookheimer SY, Strojwas MH, Cohen MS, Saunders AM, Pericak-Vance MA et al. 2000. Patterns of brain activation in people at risk for Alzheimer's disease. N. Engl. J. Med. 343:450–56
    [Google Scholar]
  11. Borlikova GG, Trejo M, Mably AJ, Mc Donald JM, Sala Frigerio C et al. 2013. Alzheimer brain-derived amyloid β-protein impairs synaptic remodeling and memory consolidation. Neurobiol. Aging 34:1315–27
    [Google Scholar]
  12. Born HA 2015. Seizures in Alzheimer's disease. Neuroscience 286:251–63
    [Google Scholar]
  13. Braak H, Braak E 1991. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–59
    [Google Scholar]
  14. Buckley RF, Schultz AP, Hedden T, Papp KV, Hanseeuw BJ et al. 2017. Functional network integrity presages cognitive decline in preclinical Alzheimer disease. Neurology 89:29–37
    [Google Scholar]
  15. Buckner RL, Andrews-Hanna JR, Schacter DL 2008. The brain's default network: anatomy, function, and relevance to disease. Ann. N. Y. Acad. Sci. 1124:1–38
    [Google Scholar]
  16. Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R et al. 2005. Molecular, structural, and functional characterization of Alzheimer's disease: evidence for a relationship between default activity, amyloid, and memory. J. Neurosci. 25:7709–17
    [Google Scholar]
  17. Busche MA, Chen X, Henning HA, Reichwald J, Staufenbiel M et al. 2012. Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer's disease. PNAS 109:8740–45
    [Google Scholar]
  18. Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH et al. 2008. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science 321:1686–89
    [Google Scholar]
  19. Busche MA, Grienberger C, Keskin AD, Song B, Neumann U et al. 2015a. Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimer's models. Nat. Neurosci. 18:1725–27
    [Google Scholar]
  20. Busche MA, Kekuš M, Adelsberger H, Noda T, Förstl H et al. 2015b. Rescue of long-range circuit dysfunction in Alzheimer's disease models. Nat. Neurosci. 18:1623–30
    [Google Scholar]
  21. Busche MA, Konnerth A 2015. Neuronal hyperactivity–a key defect in Alzheimer's disease. BioEssays 37:624–32
    [Google Scholar]
  22. Busche MA, Konnerth A 2016. Impairments of neural circuit function in Alzheimer's disease. Philos. Trans. R. Soc. B 371:20150429
    [Google Scholar]
  23. Chhatwal JP, Schultz AP, Johnson K, Benzinger TLS, Jack C et al. 2013. Impaired default network functional connectivity in autosomal dominant Alzheimer disease. Neurology 81:736–44
    [Google Scholar]
  24. Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu F et al. 2014. Early clinical PET imaging results with the novel PHF-tau radioligand F18-T808. J. Alzheimers Dis. 38:171–84
    [Google Scholar]
  25. Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR et al. 2005. Synaptic activity regulates interstitial fluid amyloid-β levels in vivo. Neuron 48:913–22
    [Google Scholar]
  26. Clemens Z, Fabó D, Halász P 2005. Overnight verbal memory retention correlates with the number of sleep spindles. Neuroscience 132:529–35
    [Google Scholar]
  27. D'Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S et al. 2011. Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer's disease. Nat. Neurosci. 14:69–76
    [Google Scholar]
  28. Damoiseaux JS, Prater KE, Miller BL, Greicius MD 2012. Functional connectivity tracks clinical deterioration in Alzheimer's disease. Neurobiol. Aging 33:828.e19–30
    [Google Scholar]
  29. Daselaar SM, Prince SE, Cabeza R 2004. When less means more: deactivations during encoding that predict subsequent memory. NeuroImage 23:921–27
    [Google Scholar]
  30. DeKosky ST, Scheff SW, Styren SD 1996. Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5:417–21
    [Google Scholar]
  31. Devanand DP, Pradhaban G, Liu X, Khandji A, De Santi S et al. 2007. Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer's disease. Neurology 68:828–36
    [Google Scholar]
  32. Dickerson BC, Salat DH, Greve DN, Chua EF, Rand-Giovannetti E et al. 2005. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65:404–11
    [Google Scholar]
  33. Diekelmann S, Born J 2010. The memory function of sleep. Nat. Rev. Neurosci. 11:114–26
    [Google Scholar]
  34. Dillen KNH, Jacobs HIL, Kukolja J, Richter N, von Reutern B et al. 2017. Functional disintegration of the default mode network in prodromal Alzheimer's disease. J. Alzheimers Dis. 59:169–87
    [Google Scholar]
  35. Dolev I, Fogel H, Milshtein H, Berdichevsky Y, Lipstein N et al. 2013. Spike bursts increase amyloid-β 40/42 ratio by inducing a presenilin-1 conformational change. Nat. Neurosci. 16:587–95
    [Google Scholar]
  36. Drzezga A, Becker JA, van Dijk KRA, Sreenivasan A, Talukdar T et al. 2011. Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden. Brain 134:Pt. 61635–46
    [Google Scholar]
  37. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL et al. 2014. Advancing research diagnostic criteria for Alzheimer's disease. The IWG-2 criteria. Lancet Neurol 13:614–29
    [Google Scholar]
  38. Eichenbaum H 2017. Memory: organization and control. Annu. Rev. Psychol. 68:19–45
    [Google Scholar]
  39. Ferris SH, de Leon MJ, Wolf AP, Farkas T, Christman DR et al. 1980. Positron emission tomography in the study of aging and senile dementia. Neurobiol. Aging 1:127–31
    [Google Scholar]
  40. Ficca G, Lombardo P, Rossi L, Salzarulo P 2000. Morning recall of verbal material depends on prior sleep organization. Behav. Brain Res. 112:159–63
    [Google Scholar]
  41. Fletcher E, Raman M, Huebner P, Liu A, Mungas D et al. 2013. Loss of fornix white matter volume as a predictor of cognitive impairment in cognitively normal elderly individuals. JAMA Neurol 70:1389–95
    [Google Scholar]
  42. Fogel H, Frere S, Segev O, Bharill S, Shapira I et al. 2014. APP homodimers transduce an amyloid-β-mediated increase in release probability at excitatory synapses. Cell Rep 7:1560–76
    [Google Scholar]
  43. Freir DB, Holscher C, Herron CE 2001. Blockade of long-term potentiation by β-amyloid peptides in the CA1 region of the rat hippocampus in vivo. J. Neurophysiol. 85:708–13
    [Google Scholar]
  44. Greicius MD, Srivastava G, Reiss AL, Menon V 2004. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. PNAS 101:4637–42
    [Google Scholar]
  45. Grienberger C, Rochefort NL, Adelsberger H, Henning HA, Hill DN et al. 2012. Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease. Nat. Commun. 3:774
    [Google Scholar]
  46. Hardy J, Selkoe DJ 2002. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353–56
    [Google Scholar]
  47. Hedden T, van Dijk KRA, Becker JA, Mehta A, Sperling RA et al. 2009. Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J. Neurosci. 29:12686–94
    [Google Scholar]
  48. Helfrich RF, Mander BA, Jagust WJ, Knight RT, Walker MP 2018. Old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting. Neuron 97:221–30.e224
    [Google Scholar]
  49. Hita-Yañez E, Atienza M, Gil-Neciga E, Cantero JL 2012. Disturbed sleep patterns in elders with mild cognitive impairment: the role of memory decline and ApoE ε4 genotype. Curr. Alzheimer Res. 9:290–97
    [Google Scholar]
  50. Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S et al. 2016. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352:712–16
    [Google Scholar]
  51. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G et al. 1999. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. PNAS 96:3228–33
    [Google Scholar]
  52. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T et al. 2006. AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss. Neuron 52:831–43
    [Google Scholar]
  53. Huang Y, Potter R, Sigurdson W, Santacruz A, Shih S et al. 2012. Effects of age and amyloid deposition on Aβ dynamics in the human central nervous system. Arch. Neurol. 69:51–58
    [Google Scholar]
  54. Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM et al. 2015. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression. Brain 138:Pt. 41023–35
    [Google Scholar]
  55. Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F et al. 2016. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540:230–35
    [Google Scholar]
  56. Jack CR Jr., Albert MS, Knopman DS, McKhann GM, Sperling RA et al. 2011. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7:257–62
    [Google Scholar]
  57. Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R et al. 2006. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. PNAS 103:5161–66
    [Google Scholar]
  58. Jeong J 2004. EEG dynamics in patients with Alzheimer's disease. Clin. Neurophysiol. 115:1490–505
    [Google Scholar]
  59. Jin M, Shepardson N, Yang T, Chen G, Walsh D, Selkoe DJ 2011. Soluble amyloid β-protein dimers isolated from Alzheimer cortex directly induce tau hyperphosphorylation and neuritic degeneration. PNAS 108:5819–24
    [Google Scholar]
  60. Johnson KA, Schultz A, Betensky RA, Becker JA, Sepulcre J et al. 2016. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Ann. Neurol. 79:110–19
    [Google Scholar]
  61. Jones DT, Knopman DS, Gunter JL, Graff-Radford J, Vemuri P et al. 2016. Cascading network failure across the Alzheimer's disease spectrum. Brain 139:Pt. 2547–62
    [Google Scholar]
  62. Ju Y-ES, McLeland JS, Toedebusch CD, Xiong C, Fagan AM et al. 2013. Sleep quality and preclinical Alzheimer disease. JAMA Neurol 70:587–93
    [Google Scholar]
  63. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D et al. 2003. APP processing and synaptic function. Neuron 37:925–37
    [Google Scholar]
  64. Kang J-E, Lim MM, Bateman RJ, Lee JJ, Smyth LP et al. 2009. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science 326:1005–7
    [Google Scholar]
  65. Kastanenka KV, Hou SS, Shakerdge N, Logan R, Feng D et al. 2017. Optogenetic restoration of disrupted slow oscillations halts amyloid deposition and restores calcium homeostasis in an animal model of Alzheimer's disease. PLOS ONE 12:e0170275
    [Google Scholar]
  66. Keage HAD, Banks S, Yang KL, Morgan K, Brayne C, Matthews FE 2012. What sleep characteristics predict cognitive decline in the elderly. Sleep Med 13:886–92
    [Google Scholar]
  67. Keskin AD, Kekuš M, Adelsberger H, Neumann U, Shimshek DR et al. 2017. BACE inhibition-dependent repair of Alzheimer's pathophysiology. PNAS 114:8631–36
    [Google Scholar]
  68. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G et al. 2004. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Ann. Neurol. 55:306–19
    [Google Scholar]
  69. Klyubin I, Betts V, Welzel AT, Blennow K, Zetterberg H et al. 2008. Amyloid β protein dimer-containing human CSF disrupts synaptic plasticity: prevention by systemic passive immunization. J. Neurosci. 28:4231–37
    [Google Scholar]
  70. Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML et al. 2009. Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. PNAS 106:4012–17
    [Google Scholar]
  71. Koh MT, Haberman RP, Foti S, McCown TJ, Gallagher M 2010. Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment. Neuropsychopharmacology 5:1016–25
    [Google Scholar]
  72. Kuchibhotla KV, Goldman ST, Lattarulo CR, Wu HY, Hyman BT, Bacskai BJ 2008. Aβ plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 59:214–25
    [Google Scholar]
  73. Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ 2009. Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323:1211–15
    [Google Scholar]
  74. Ladenbauer J, Ladenbauer J, Külzow N, de Boor R, Avramova E et al. 2017. Promoting sleep oscillations and their functional coupling by transcranial stimulation enhances memory consolidation in mild cognitive impairment. J. Neurosci. 37:7111–24
    [Google Scholar]
  75. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R et al. 1998. Diffusible, nonfibrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. PNAS 95:6448–53
    [Google Scholar]
  76. Lanz TA, Carter DB, Merchant KM 2003. Dendritic spine loss in the hippocampus of young PDAPP and Tg2576 mice and its prevention by the ApoE2 genotype. Neurobiol. Dis. 13:246–53
    [Google Scholar]
  77. Leal SL, Landau SM, Bell RK, Jagust WJ 2017. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline. eLife 6:e22978
    [Google Scholar]
  78. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG et al. 2006. A specific amyloid-β protein assembly in the brain impairs memory. Nature 440:352–57
    [Google Scholar]
  79. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D 2009. Soluble oligomers of amyloid β protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62:788–801
    [Google Scholar]
  80. Liebscher S, Keller GB, Goltstein PM, Bonhoeffer T, Hübener M 2016. Selective persistence of sensorimotor mismatch signals in visual cortex of behaving Alzheimer's disease mice. Curr. Biol. 26:956–64
    [Google Scholar]
  81. Liguori C, Romigi A, Nuccetelli M, Zannino S, Sancesario G et al. 2014. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol 71:1498–505
    [Google Scholar]
  82. Lim ASP, Kowgier M, Yu L, Buchman AS, Bennett DA 2013a. Sleep fragmentation and the risk of incident Alzheimer's disease and cognitive decline in older persons. Sleep 36:1027–32
    [Google Scholar]
  83. Lim ASP, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA 2013b. Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer's disease and neurofibrillary tangle density by sleep. JAMA Neurol 70:1544–51
    [Google Scholar]
  84. Liu Y, Yu C, Zhang X, Liu J, Duan Y et al. 2014. Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease. Cereb. Cortex 24:1422–35
    [Google Scholar]
  85. Lu H, Zou Q, Gu H, Raichle ME, Stein EA, Yang Y 2012. Rat brains also have a default mode network. PNAS 109:3979–84
    [Google Scholar]
  86. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y et al. 1999. Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease. Am. J. Pathol. 155:853–62
    [Google Scholar]
  87. Lustig C, Snyder AZ, Bhakta M, O'Brien KC, McAvoy M et al. 2003. Functional deactivations: change with age and dementia of the Alzheimer type. PNAS 100:14504–9
    [Google Scholar]
  88. Maier FC, Wehrl HF, Schmid AM, Mannheim JG, Wiehr S et al. 2014. Longitudinal PET-MRI reveals β-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion. Nat. Med. 20:1485–92
    [Google Scholar]
  89. Mander BA, Marks SM, Vogel JW, Rao V, Lu B et al. 2015. β-Amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation. Nat. Neurosci. 18:1051–57
    [Google Scholar]
  90. Mander BA, Rao V, Lu B, Saletin JM, Ancoli-Israel S et al. 2014. Impaired prefrontal sleep spindle regulation of hippocampal-dependent learning in older adults. Cereb. Cortex 24:3301–9
    [Google Scholar]
  91. Marshall L, Helgadóttir H, Mölle M, Born J 2006. Boosting slow oscillations during sleep potentiates memory. Nature 444:610–13
    [Google Scholar]
  92. Masliah E, Mallory M, Hansen L, DeTeresa R, Alford M, Terry R 1994. Synaptic and neuritic alterations during the progression of Alzheimer's disease. Neurosci. Lett. 174:67–72
    [Google Scholar]
  93. Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T et al. 2010. Decreased clearance of CNS β-amyloid in Alzheimer's disease. Science 330:1774
    [Google Scholar]
  94. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR et al. 2011. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7:263–69
    [Google Scholar]
  95. Mednick S, Nakayama K, Stickgold R 2003. Sleep-dependent learning: A nap is as good as a night. Nat. Neurosci. 6:697–98
    [Google Scholar]
  96. Mednick SC, McDevitt EA, Walsh JK, Wamsley E, Paulus M et al. 2013. The critical role of sleep spindles in hippocampal-dependent memory: a pharmacology study. J. Neurosci. 33:4494–504
    [Google Scholar]
  97. Mhatre SD, Tsai CA, Rubin AJ, James ML, Andreasson KI 2015. Microglial malfunction: the third rail in the development of Alzheimer's disease. Trends Neurosci 38:621–36
    [Google Scholar]
  98. Miller SL, Celone K, DePeau K, Diamond E, Dickerson BC et al. 2008. Age-related memory impairment associated with loss of parietal deactivation but preserved hippocampal activation. PNAS 105:2181–86
    [Google Scholar]
  99. Mormino EC, Brandel MG, Madison CM, Marks S, Baker SL, Jagust WJ 2012. Aβ deposition in aging is associated with increases in brain activation during successful memory encoding. Cereb. Cortex 22:1813–23
    [Google Scholar]
  100. Morris E, Chalkidou A, Hammers A, Peacock J, Summers J, Keevil S 2016. Diagnostic accuracy of 18F amyloid PET tracers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Eur. J. Nucl. Med. Mol. Imaging 43:374–85
    [Google Scholar]
  101. Müller T, Meyer HE, Egensperger R, Marcus K 2008. The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease. Prog. Neurobiol. 85:393–406
    [Google Scholar]
  102. Müller UC, Deller T, Korte M 2017. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat. Rev. Neurosci. 18:281–98
    [Google Scholar]
  103. Murphy M, Riedner BA, Huber R, Massimini M, Ferrarelli F, Tononi G 2009. Source modeling sleep slow waves. PNAS 106:1608–13
    [Google Scholar]
  104. Myers N, Pasquini L, Göttler J, Grimmer T, Koch K et al. 2014. Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer's disease. Brain 137:Pt. 72052–64
    [Google Scholar]
  105. Neumann U, Rueeger H, Machauer R, Veenstra SJ, Lueoend RM et al. 2015. A novel BACE inhibitor NB-360 shows a superior pharmacological profile and robust reduction of amyloid-β and neuroinflammation in APP transgenic mice. Mol. Neurodegener. 10:44
    [Google Scholar]
  106. Ngo H-VV, Martinetz T, Born J, Mölle M 2013. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron 78:545–53
    [Google Scholar]
  107. Nir TM, Jahanshad N, Villalon-Reina JE, Toga AW, Jack CR et al. 2013. Effectiveness of regional DTI measures in distinguishing Alzheimer's disease, MCI, and normal aging. NeuroImage 3:180–95
    [Google Scholar]
  108. O'Brien JL, O'Keefe KM, LaViolette PS, DeLuca AN, Blacker D et al. 2010. Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology 74:1969–76
    [Google Scholar]
  109. Ooms S, Overeem S, Besse K, Rikkert MO, Verbeek M et al. 2014. Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men: a randomized clinical trial. JAMA Neurol 71:971–77
    [Google Scholar]
  110. Palmqvist S, Schöll M, Strandberg O, Mattsson N, Stomrud E et al. 2017. Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity. Nat. Commun. 8:1214
    [Google Scholar]
  111. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT et al. 2007. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55:697–711
    [Google Scholar]
  112. Palop JJ, Mucke L 2016. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 17:777–92
    [Google Scholar]
  113. Pariente J, Cole S, Henson R, Clare L, Kennedy A et al. 2005. Alzheimer's patients engage an alternative network during a memory task. Ann. Neurol. 58:870–79
    [Google Scholar]
  114. Peigneux P, Laureys S, Fuchs S, Collette F, Perrin F et al. 2004. Are spatial memories strengthened in the human hippocampus during slow wave sleep. Neuron 44:535–45
    [Google Scholar]
  115. Pekny M, Pekna M, Messing A, Steinhauser C, Lee JM et al. 2016. Astrocytes: a central element in neurological diseases. Acta Neuropathol 131:323–45
    [Google Scholar]
  116. Persson J, Lind J, Larsson A, Ingvar M, Sleegers K et al. 2008. Altered deactivation in individuals with genetic risk for Alzheimer's disease. Neuropsychologia 46:1679–87
    [Google Scholar]
  117. Pihlajamäki M, O'Keefe K, Bertram L, Tanzi RE, Dickerson BC et al. 2010. Evidence of altered posteromedial cortical FMRI activity in subjects at risk for Alzheimer disease. Alzheimer Dis. Assoc. Disord. 24:28–36
    [Google Scholar]
  118. Prinz M, Priller J, Sisodia SS, Ransohoff RM 2011. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat. Neurosci. 14:1227–35
    [Google Scholar]
  119. Puzzo D, Privitera L, Leznik E, Fa M, Staniszewski A et al. 2008. Picomolar amyloid-β positively modulates synaptic plasticity and memory in hippocampus. J. Neurosci. 28:14537–45
    [Google Scholar]
  120. Quiroz YT, Budson AE, Celone K, Ruiz A, Newmark R et al. 2010. Hippocampal hyperactivation in presymptomatic familial Alzheimer's disease. Ann. Neurol. 68:865–75
    [Google Scholar]
  121. Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL 2001. A default mode of brain function. PNAS 98:676–82
    [Google Scholar]
  122. Roh JH, Huang Y, Bero AW, Kasten T, Stewart FR, Bateman RJ, Holtzman DM 2012. Disruption of the sleep-wake cycle and diurnal fluctuation of β-amyloid in mice with Alzheimer's disease pathology. Sci. Transl. Med. 4:150ra122
    [Google Scholar]
  123. Roy DS, Arons A, Mitchell TI, Pignatelli M, Ryan TJ, Tonegawa S 2016. Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease. Nature 531:508–12
    [Google Scholar]
  124. Rudinskiy N, Hawkes JM, Betensky RA, Eguchi M, Yamaguchi S et al. 2012. Orchestrated experience-driven Arc responses are disrupted in a mouse model of Alzheimer's disease. Nat. Neurosci. 15:1422–29
    [Google Scholar]
  125. Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG et al. 2012. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. PNAS 109:E2895–903
    [Google Scholar]
  126. Sanchez-Espinosa MP, Atienza M, Cantero JL 2014. Sleep deficits in mild cognitive impairment are related to increased levels of plasma amyloid-β and cortical thinning. NeuroImage 98:395–404
    [Google Scholar]
  127. Scala F, Fusco S, Ripoli C, Piacentini R, Li Puma DD et al. 2015. Intraneuronal Aβ accumulation induces hippocampal neuron hyperexcitability through A-type K+ current inhibition mediated by activation of caspases and GSK-3. Neurobiol. Aging 36:886–900
    [Google Scholar]
  128. Scarmeas N, Honig LS, Choi H, Cantero J, Brandt J et al. 2009. Seizures in Alzheimer disease: who, when, and how common. Arch. Neurol. 66:992–97
    [Google Scholar]
  129. Seab JP, Jagust WJ, Wong ST, Roos MS, Reed BR, Budinger TF 1988. Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease. Magn. Reson. Med. 8:200–8
    [Google Scholar]
  130. Selkoe DJ 2002. Alzheimer's disease is a synaptic failure. Science 298:789–91
    [Google Scholar]
  131. Selkoe DJ, Hardy J 2016. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol. Med. 8:595–608
    [Google Scholar]
  132. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT 2011. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med. 1:a006189
    [Google Scholar]
  133. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL 2007. Natural oligomers of the Alzheimer amyloid-β protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci. 27:2866–75
    [Google Scholar]
  134. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE et al. 2008. Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 14:837–42
    [Google Scholar]
  135. Sheline YI, Morris JC, Snyder AZ, Price JL, Yan Z et al. 2010a. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Aβ42. J. Neurosci. 30:17035–40
    [Google Scholar]
  136. Sheline YI, Raichle ME, Snyder AZ, Morris JC, Head D et al. 2010b. Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol. Psychiatry 67:584–87
    [Google Scholar]
  137. Siskova Z, Justus D, Kaneko H, Friedrichs D, Henneberg N et al. 2014. Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease. Neuron 84:1023–33
    [Google Scholar]
  138. Sperling R, Chua E, Cocchiarella A, Rand-Giovannetti E, Poldrack R et al. 2003. Putting names to faces: Successful encoding of associative memories activates the anterior hippocampal formation. NeuroImage 20:1400–10
    [Google Scholar]
  139. Sperling RA, Dickerson BC, Pihlajamaki M, Vannini P, LaViolette PS et al. 2010. Functional alterations in memory networks in early Alzheimer's disease. Neuromol. Med. 12:27–43
    [Google Scholar]
  140. Sperling RA, Laviolette PS, O'Keefe K, O'Brien J, Rentz DM et al. 2009. Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 63:178–88
    [Google Scholar]
  141. Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM et al. 2013. Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol 70:1537–43
    [Google Scholar]
  142. Spires TL, Meyer-Luehmann M, Stern EA, McLean PJ, Skoch J et al. 2005. Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J. Neurosci. 25:7278–87
    [Google Scholar]
  143. Sprecher KE, Koscik RL, Carlsson CM, Zetterberg H, Blennow K et al. 2017. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology 89:445–53
    [Google Scholar]
  144. Staresina BP, Bergmann TO, Bonnefond M, van der Meij R, Jensen O et al. 2015. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep. Nat. Neurosci. 18:1679–86
    [Google Scholar]
  145. Steriade M 2006. Grouping of brain rhythms in corticothalamic systems. Neuroscience 137:1087–106
    [Google Scholar]
  146. Steriade M, Nuñez A, Amzica F 1993. A novel slow (<1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J. Neurosci. 13:3252–65
    [Google Scholar]
  147. Tahmasian M, Pasquini L, Scherr M, Meng C, Förster S et al. 2015. The lower hippocampus global connectivity, the higher its local metabolism in Alzheimer disease. Neurology 84:1956–63
    [Google Scholar]
  148. Takashima A, Petersson KM, Rutters F, Tendolkar I, Jensen O et al. 2006. Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study. PNAS 103:756–61
    [Google Scholar]
  149. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R et al. 1991. Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30:572–80
    [Google Scholar]
  150. Thal DR, Rüb U, Orantes M, Braak H 2002. Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–800
    [Google Scholar]
  151. Uddin LQ, Kelly AM, Biswal BB, Castellanos FX, Milham MP 2009. Functional connectivity of default mode network components: correlation, anticorrelation, and causality. Hum. Brain Mapp. 30:625–37
    [Google Scholar]
  152. Utevsky AV, Smith DV, Huettel SA 2014. Precuneus is a functional core of the default-mode network. J. Neurosci. 34:932–40
    [Google Scholar]
  153. Van Der Werf YD, Altena E, Schoonheim MM, Sanz-Arigita EJ, Vis JC et al. 2009. Sleep benefits subsequent hippocampal functioning. Nat. Neurosci. 12:122
    [Google Scholar]
  154. Verret L, Mann EO, Hang GB, Barth AM, Cobos I et al. 2012. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149:708–21
    [Google Scholar]
  155. Vossel KA, Ranasinghe KG, Beagle AJ, Mizuiri D, Honma SM et al. 2016. Incidence and impact of subclinical epileptiform activity in Alzheimer's disease. Ann. Neurol. 80:858–70
    [Google Scholar]
  156. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R et al. 2002. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535–39
    [Google Scholar]
  157. Wang L, Zang Y, He Y, Liang M, Zhang X et al. 2006. Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state fMRI. NeuroImage 31:496–504
    [Google Scholar]
  158. Ward AM, Schultz AP, Huijbers W, van Dijk KRA, Hedden T, Sperling RA 2014. The parahippocampal gyrus links the default-mode cortical network with the medial temporal lobe memory system. Hum. Brain Mapp. 35:1061–73
    [Google Scholar]
  159. Wei M, Zhao B, Huo K, Deng Y, Shang S et al. 2017. Sleep deprivation induced plasma amyloid-β transport disturbance in healthy young adults. J. Alzheimers Dis. 57:899–906
    [Google Scholar]
  160. Wei W, Nguyen LN, Kessels HW, Hagiwara H, Sisodia S, Malinow R 2010. Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nat. Neurosci. 13:190–96
    [Google Scholar]
  161. Westerberg CE, Lundgren EM, Florczak SM, Mesulam M-M, Weintraub S et al. 2010. Sleep influences the severity of memory disruption in amnestic mild cognitive impairment: results from sleep self-assessment and continuous activity monitoring. Alzheimer Dis. Assoc. Disord. 24:325–33
    [Google Scholar]
  162. Westerberg CE, Mander BA, Florczak SM, Weintraub S, Mesulam M-M et al. 2012. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. J. Int. Neuropsychol. Soc. 18:490–500
    [Google Scholar]
  163. Willem M, Tahirovic S, Busche MA, Ovsepian SV, Chafai M et al. 2015. η-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature 526:443–47
    [Google Scholar]
  164. Wilson IA, Ikonen S, Gallagher M, Eichenbaum H, Tanila H 2005. Age-associated alterations of hippocampal place cells are subregion specific. J. Neurosci. 25:6877–86
    [Google Scholar]
  165. Wilson MA, McNaughton BL 1994. Reactivation of hippocampal ensemble memories during sleep. Science 265:676–79
    [Google Scholar]
  166. Xie L, Kang H, Xu Q, Chen MJ, Liao Y et al. 2013. Sleep drives metabolite clearance from the adult brain. Science 342:373–77
    [Google Scholar]
  167. Xu W, Fitzgerald S, Nixon RA, Levy E, Wilson DA 2015. Early hyperactivity in lateral entorhinal cortex is associated with elevated levels of AβPP metabolites in the Tg2576 mouse model of Alzheimer's disease. Exp. Neurol. 264:82–91
    [Google Scholar]
  168. Yang T, Li S, Xu H, Walsh DM, Selkoe DJ 2017. Large soluble oligomers of amyloid β-protein from Alzheimer brain are far less neuroactive than the smaller oligomers to which they dissociate. J. Neurosci. 37:152–63
    [Google Scholar]
  169. Yassa MA, Lacy JW, Stark SM, Albert MS, Gallagher M, Stark CEL 2011. Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults. Hippocampus 21:968–79
    [Google Scholar]
  170. Yuan P, Grutzendler J 2016. Attenuation of β-amyloid deposition and neurotoxicity by chemogenetic modulation of neural activity. J. Neurosci. 36:632–41
    [Google Scholar]
  171. Zeineh MM, Engel SA, Thompson PM, Bookheimer SY 2003. Dynamics of the hippocampus during encoding and retrieval of face-name pairs. Science 299:577–80
    [Google Scholar]
  172. Zhao Q-F, Tan L, Wang H-F, Jiang T, Tan M-S et al. 2016. The prevalence of neuropsychiatric symptoms in Alzheimer's disease: systematic review and meta-analysis. J. Aff. Disord. 190:264–71
    [Google Scholar]
  173. Zhou Y, Dougherty JH Jr., Hubner KF, Bai B, Cannon RL, Hutson RK 2008. Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment. Alzheimer Dement. 4:265–70
    [Google Scholar]
/content/journals/10.1146/annurev-neuro-080317-061725
Loading
/content/journals/10.1146/annurev-neuro-080317-061725
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error