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A network dysfunction perspective on neurodegenerative diseases

Abstract

Patients with Alzheimer's disease or other neurodegenerative disorders show remarkable fluctuations in neurological functions, even during the same day. These fluctuations cannot be caused by sudden loss or gain of nerve cells. Instead, it is likely that they reflect variations in the activity of neural networks and, perhaps, chronic intoxication by abnormal proteins that the brain is temporarily able to overcome. These ideas have far-reaching therapeutic implications.

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Figure 1: Neurodegenerative disorders affect neural activities at many levels.
Figure 2: Functional fluctuations in neurodegenerative disorders may represent fruitful entry points for mechanistic investigations and clinical trials.
Figure 3: Neural plasticity counteracts neurodegenerative disorders at multiple levels.

References

  1. Cowan, W. M. & Kandel, E. R. Prospects for neurology and psychiatry. J. Am. Med. Assoc. 285, 594–600 (2001).

    CAS  Google Scholar 

  2. Bradshaw, J., Saling, M., Hopwood, M., Anderson, V. & Brodtmann, A. Fluctuating cognition in dementia with Lewy bodies and Alzheimer's disease is qualitatively distinct. J. Neurol. Neurosurg. Psychiatry 75, 382–387 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Walker, M. P. et al. The clinician assessment of fluctuation and the one day fluctuation assessment scale. Two methods to assess fluctuating confusion in dementia. Br. J. Psychiatry 177, 252–256 (2000).

    CAS  PubMed  Google Scholar 

  4. Walker, M. P. et al. Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. Neurology 54, 1616–1625 (2000).

    CAS  PubMed  Google Scholar 

  5. McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65, 1863–1872 (2005).

    CAS  PubMed  Google Scholar 

  6. Robertsson, B., Blennow, K., Gottfries, C. G. & Wallin, A. Delirium in dementia. Int. J. Geriatr. Psychiatry 13, 49–56 (1998).

    CAS  PubMed  Google Scholar 

  7. Terry, R. D. et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30, 572–580 (1991).

    CAS  PubMed  Google Scholar 

  8. Morrison, J. H. & Hof, P. R. Life and death of neurons in the aging brain. Science 278, 412–419 (1997).

    ADS  CAS  PubMed  Google Scholar 

  9. Kordower, J. H. et al. Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann. Neurol. 49, 202–213 (2001).

    CAS  PubMed  Google Scholar 

  10. Price, J. L. et al. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch. Neurol. 58, 1395–1402 (2001).

    CAS  PubMed  Google Scholar 

  11. Greffard, S. et al. Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra. Arch. Neurol. 63, 584–588 (2006).

    PubMed  Google Scholar 

  12. Blanchet, P. J. Antipsychotic drug-induced movement disorders. Can. J. Neurol. Sci. 30 (Suppl. 1), S101–S107 (2003).

    PubMed  Google Scholar 

  13. Martino, D. & Giovannoni, G. Antibasal ganglia antibodies and their relevance to movement disorders. Curr. Opin. Neurol. 17, 425–432 (2004).

    PubMed  Google Scholar 

  14. Lewin, R. Is your brain really necessary? Science 210, 1232–1234 (1980).

    ADS  CAS  PubMed  Google Scholar 

  15. Chen, R., Cohen, L. G. & Hallett, M. Nervous system reorganization following injury. Neuroscience 111, 761–773 (2002).

    CAS  PubMed  Google Scholar 

  16. Bezard, E., Gross, C. E. & Brotchie, J. M. Presymptomatic compensation in Parkinson's disease is not dopamine-mediated. Trends Neurosci. 26, 215–221 (2003).

    CAS  PubMed  Google Scholar 

  17. Stern, Y. What is cognitive reserve? Theory and research application of the reserve concept. J. Int. Neuropsychol. Soc. 8, 448–460 (2002).

    PubMed  Google Scholar 

  18. Buckner, R. L. Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron 44, 195–208 (2004).

    CAS  PubMed  Google Scholar 

  19. Iaria, G., Petrides, M., Dagher, A., Pike, B. & Bohbot, V. D. Cognitive strategies dependent on the hippocampus and caudate nucleus in human navigation: variability and change with practice. J. Neurosci. 23, 5945–5952 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Maguire, E. A., Valentine, E. R., Wilding, J. M. & Kapur, N. Routes to remembering: the brains behind superior memory. Nature Neurosci. 6, 90–95 (2003).

    CAS  PubMed  Google Scholar 

  21. Mahley, R. W., Weisgraber, K. H. & Huang, Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc. Natl Acad. Sci. USA 103, 5644–5651 (2006).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zlokovic, B. V. Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci. 28, 202–208 (2005).

    CAS  PubMed  Google Scholar 

  23. Prinz, A. A., Bucher, D. & Marder, E. Similar network activity from disparate circuit parameters. Nature Neurosci. 7, 1345–1352 (2004).

    CAS  PubMed  Google Scholar 

  24. Edelman, G. M. & Gally, J. A. Degeneracy and complexity in biological systems. Proc. Natl Acad. Sci. USA 98, 13763–13768 (2001).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  25. Whone, A. L., Moore, R. Y., Piccini, P. P. & Brooks, D. J. Plasticity of the nigropallidal pathway in Parkinson's disease. Ann. Neurol. 53, 206–213 (2003).

    PubMed  Google Scholar 

  26. Walsh, D. M. & Selkoe, D. J. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron 44, 181–193 (2004).

    CAS  PubMed  Google Scholar 

  27. Muchowski, P. J. & Wacker, J. L. Modulation of neurodegeneration by molecular chaperones. Nature Rev. Neurosci. 6, 11–22 (2005).

    CAS  Google Scholar 

  28. Mark, R. J., Ashford, J. W., Goodman, Y. & Mattson, M. P. Anticonvulsants attenuate amyloid β-peptide neurotoxicity, Ca2+ deregulation, and cytoskeletal pathology. Neurobiol. Aging 16, 187–198 (1995).

    CAS  PubMed  Google Scholar 

  29. Hynd, M. R., Scott, H. L. & Dodd, P. R. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem. Int. 45, 583–595 (2004).

    CAS  PubMed  Google Scholar 

  30. Wyss-Coray, T. & Mucke, L. Inflammation in neurodegenerative disease — a double-edged sword. Neuron 35, 419–432 (2002).

    CAS  PubMed  Google Scholar 

  31. Beal, M. F. Mitochondria take center stage in aging and neurodegeneration. Ann. Neurol. 58, 495–505 (2005).

    CAS  PubMed  Google Scholar 

  32. Small, D. H., Mok, S. S. & Bornstein, J. C. Alzheimer's disease and Aβ toxicity: from top to bottom. Nature Rev. Neurosci. 2, 595–598 (2001).

    CAS  Google Scholar 

  33. Mattson, M. P. Pathways towards and away from Alzheimer's disease. Nature 430, 631–639 (2004).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  34. Handley, O. J., Naji, J. J., Dunnett, S. B. & Rosser, A. E. Pharmaceutical, cellular and genetic therapies for Huntington's disease. Clin. Sci. (Lond.) 110, 73–88 (2006).

    CAS  Google Scholar 

  35. Honer, W. G. Pathology of presynaptic proteins in Alzheimer's disease: more than simple loss of terminals. Neurobiol. Aging 24, 1047–1062 (2003).

    CAS  PubMed  Google Scholar 

  36. Levine, M. S., Cepeda, C., Hickey, M. A., Fleming, S. M. & Chesselet, M. F. Genetic mouse models of Huntington's and Parkinson's diseases: illuminating but imperfect. Trends Neurosci. 27, 691–697 (2004).

    CAS  PubMed  Google Scholar 

  37. van Dellen, A., Grote, H. E. & Hannan, A. J. Gene–environment interactions, neuronal dysfunction and pathological plasticity in Huntington's disease. Clin. Exp. Pharmacol. Physiol. 32, 1007–1019 (2005).

    CAS  PubMed  Google Scholar 

  38. Lazarov, O. et al. Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell 120, 701–713 (2005).

    CAS  PubMed  Google Scholar 

  39. Mesulam, M. M. Neuroplasticity failure in Alzheimer's disease: bridging the gap between plaques and tangles. Neuron 24, 521–529 (1999).

    CAS  PubMed  Google Scholar 

  40. Verdier, Y., Zarandi, M. & Penke, B. Amyloid β-peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease. J. Pept. Sci. 10, 229–248 (2004).

    CAS  PubMed  Google Scholar 

  41. Schmitt, H. P. Pouring oil into the fire? On the conundrum of the beneficial effects of NMDA receptor antagonists in Alzheimer disease. Psychopharmacology (Berl.) 9, 151–153 (2005).

    ADS  Google Scholar 

  42. Chen, J. et al. SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-κB signaling. J. Biol. Chem. 280, 40364–40374 (2005).

    CAS  PubMed  Google Scholar 

  43. Giorgini, F., Guidetti, P., Nguyen, Q., Bennett, S. C. & Muchowski, P. J. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nature Genet. 37, 526–531 (2005).

    CAS  PubMed  Google Scholar 

  44. Eddleston, M. P. & Mucke, L. Molecular profile of reactive astrocytes — implications for their role in neurologic disease. Neuroscience 54, 15–36 (1993).

    CAS  PubMed  Google Scholar 

  45. Palop, J. J. et al. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc. Natl Acad. Sci. USA 100, 9572–9577 (2003).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  46. Drzezga, A. et al. Impaired cross-modal inhibition in Alzheimer disease. PLoS Med. 2, 986–995 (2005).

    Google Scholar 

  47. Palop, J. J. et al. Vulnerability of dentate granule cells to disruption of Arc expression in human amyloid precursor protein transgenic mice. J. Neurosci. 25, 9686–9693 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Colom, L. V. Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease. J. Neurochem. 96, 609–623 (2006).

    CAS  PubMed  Google Scholar 

  49. Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R. & Finkbeiner, S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805–810 (2004).

    ADS  CAS  PubMed  Google Scholar 

  50. Graf, R. A. & Kater, S. B. Inhibitory neuronal activity can compensate for adverse effects of β-amyloid in hippocampal neurons. Brain Res. 786, 115–121 (1998).

    CAS  PubMed  Google Scholar 

  51. Watanabe, D. et al. Ablation of cerebellar Golgi cells disrupts synaptic integration involving GABA inhibition and NMDA receptor activation in motor coordination. Cell 95, 17–27 (1998).

    CAS  PubMed  Google Scholar 

  52. DeKosky, S. T. et al. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann. Neurol. 51, 145–155 (2002).

    CAS  PubMed  Google Scholar 

  53. Small, D. H. Do acetylcholinesterase inhibitors boost synaptic scaling in Alzheimer's disease? Trends Neurosci. 27, 245–249 (2004).

    CAS  PubMed  Google Scholar 

  54. Dickerson, B. C. et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65, 404–411 (2005).

    CAS  PubMed  Google Scholar 

  55. Oldstone, M. B. Molecular mimicry, microbial infection, and autoimmune disease: evolution of the concept. Curr. Top. Microbiol. Immunol. 296, 1–17 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Duncan, J. S., Sander, J. W., Sisodiya, S. M. & Walker, M. C. Adult epilepsy. Lancet 367, 1087–1100 (2006).

    PubMed  Google Scholar 

  57. Thompson, P. J. & Duncan, J. S. Cognitive decline in severe intractable epilepsy. Epilepsia 46, 1780–1787 (2005).

    PubMed  Google Scholar 

  58. Forsgren, L. et al. Mortality of epilepsy in developed countries: a review. Epilepsia 46 (Suppl. 11), 18–27 (2005).

    PubMed  Google Scholar 

  59. Schapira, A. H. Present and future drug treatment for Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 76, 1472–1478 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Lleo, A., Greenberg, S. M. & Growdon, J. H. Current pharmacotherapy for Alzheimer's disease. Annu. Rev. Med. 57, 513–533 (2006).

    CAS  PubMed  Google Scholar 

  61. Gsell, W., Jungkunz, G. & Riederer, P. Functional neurochemistry of Alzheimer's disease. Curr. Pharm. Des. 10, 265–293 (2004).

    CAS  PubMed  Google Scholar 

  62. Nance, M. A. & Myers, R. H. Juvenile onset Huntington's disease — clinical and research perspectives. Ment. Retard. Dev. Disabil. Res. Rev. 7, 153–157 (2001).

    CAS  PubMed  Google Scholar 

  63. Weiner, M. F. et al. Can Alzheimer's disease and dementias with Lewy bodies be distinguished clinically? J. Geriatr. Psychiatry Neurol. 16, 245–250 (2003).

    PubMed  Google Scholar 

  64. Amatniek, J. C. et al. Incidence and predictors of seizures in patients with Alzheimer's disease. Epilepsia 47, 867–872 (2006).

    PubMed  Google Scholar 

  65. Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493–506 (1996).

    CAS  PubMed  Google Scholar 

  66. Del Vecchio, R. A., Gold, L. H., Novick, S. J., Wong, G. & Hyde, L. A. Increased seizure threshold and severity in young transgenic CRND8 mice. Neurosci. Lett. 367, 164–167 (2004).

    CAS  PubMed  Google Scholar 

  67. Xie, C. W. Calcium-regulated signaling pathways: role in amyloid β-induced synaptic dysfunction. Neuromolecular Med. 6, 53–64 (2004).

    CAS  PubMed  Google Scholar 

  68. Selkoe, D. J. & Schenk, D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. 43, 545–584 (2003).

    CAS  PubMed  Google Scholar 

  69. Grady, C. L. et al. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer's disease. J. Neurosci. 2, 986–993 (2003).

    Google Scholar 

  70. Pariente, J. et al. Alzheimer's patients engage an alternative network during a memory task. Ann. Neurol. 58, 870–879 (2005).

    PubMed  Google Scholar 

  71. Nakanishi, S. Synaptic mechanisms of the cerebellar cortical network. Trends Neurosci. 28, 93–100 (2005).

    CAS  PubMed  Google Scholar 

  72. Kobayashi, D. T. & Chen, K. S. Behavioral phenotypes of amyloid-based genetically modified mouse models of Alzheimer's Disease. Genes Brain Behav. 4, 173–196 (2005).

    CAS  PubMed  Google Scholar 

  73. Janus, C. et al. Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408, 979–982 (2000).

    ADS  CAS  PubMed  Google Scholar 

  74. Morgan, D. et al. Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982–985 (2000).

    ADS  CAS  PubMed  Google Scholar 

  75. Dodart, J. C. et al. Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model. Nature Neurosci. 5, 452–457 (2002).

    CAS  PubMed  Google Scholar 

  76. Kotilinek, L. A. et al. Reversible memory loss in a mouse transgenic model of Alzheimer's disease. J. Neurosci. 22, 6331–6335 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Yamamoto, A., Lucas, J. J. & Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101, 57–66 (2000).

    CAS  PubMed  Google Scholar 

  78. Martin-Aparicio, E. et al. Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J. Neurosci. 21, 8772–8781 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Masliah, E. et al. Effects of α-synuclein immunization in a mouse model of Parkinson's disease. Neuron 46, 857–868 (2005).

    CAS  PubMed  Google Scholar 

  80. Brandt, R., Hundelt, M. & Shahani, N. Tau alteration and neuronal degeneration in tauopathies: mechanisms and models. Biochim. Biophys. Acta 1739, 331–354 (2005).

    CAS  PubMed  Google Scholar 

  81. Santacruz, K. et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science 309, 476–481 (2005).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chin, J. et al. Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J. Neurosci. 25, 9694–9703 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Dickey, C. A. et al. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci. 23, 5219–5226 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Lacor, P. N. et al. Synaptic targeting by Alzheimer's-related amyloid β oligomers. J. Neurosci. 24, 10191–10200 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Cotman, C. W., Hailer, N. P., Pfister, K. K., Soltesz, I. & Schachner, M. Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations? Prog. Neurobiol. 55, 659–669 (1998).

    CAS  PubMed  Google Scholar 

  86. Wang, Q., Walsh, D. M., Rowan, M. J., Selkoe, D. J. & Anwyl, R. Block of long-term potentiation by naturally secreted and synthetic amyloid β-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J. Neurosci. 24, 3370–3378 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Snyder, E. M. et al. Regulation of NMDA receptor trafficking by amyloid-β. Nature Neurosci. 8, 1051–1058 (2005).

    CAS  PubMed  Google Scholar 

  88. Oddo, S. & LaFerla, F. M. The role of nicotinic acetylcholine receptors in Alzheimer's disease. J. Physiol. (Paris) 99, 172–179 (2006).

    CAS  Google Scholar 

  89. Kelly, B. L., Vassar, R. & Ferreira, A. β-amyloid-induced dynamin 1 depletion in hippocampal neurons. A potential mechanism for early cognitive decline in Alzheimer disease. J. Biol. Chem. 280, 31746–31753 (2005).

    CAS  PubMed  Google Scholar 

  90. Haddad, J. J. Mitogen-activated protein kinases and the evolution of Alzheimer's: a revolutionary neurogenetic axis for therapeutic intervention? Prog. Neurobiol. 73, 359–377 (2004).

    CAS  PubMed  Google Scholar 

  91. Lee, G. Tau and src family tyrosine kinases. Biochim. Biophys. Acta 1739, 323–330 (2005).

    CAS  PubMed  Google Scholar 

  92. Giese, K. P., Ris, L. & Plattner, F. Is there a role of the cyclin-dependent kinase 5 activator p25 in Alzheimer's disease? Neuroreport 16, 1725–1730 (2005).

    CAS  PubMed  Google Scholar 

  93. Roselli, F. et al. Soluble β-amyloid1–40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses. J. Neurosci. 25, 11061–11070 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Almeida, C.G. et al. Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiol. Dis. 20, 187–198 (2005).

    CAS  PubMed  Google Scholar 

  95. Hsia, A. et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl Acad. Sci. USA 96, 3228–3233 (1999).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  96. Mucke, L. et al. High-level neuronal expression of Aβ1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 20, 4050–4058 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Moolman, D. L., Vitolo, O. V., Vonsattel, J. P. & Shelanski, M. L. Dendrite and dendritic spine alterations in Alzheimer models. J. Neurocytol. 33, 377–387 (2004).

    CAS  PubMed  Google Scholar 

  98. Kamenetz, F. et al. APP processing and synaptic function. Neuron 37, 925–937 (2003).

    CAS  PubMed  Google Scholar 

  99. Chapman, P. F. et al. Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nature Neurosci. 2, 271–276 (1999).

    CAS  PubMed  Google Scholar 

  100. Walsh, D. M. et al. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–539 (2002).

    ADS  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank S. Finkbeiner for helpful discussion of the Huntington's disease literature, J. Carroll for preparation of graphics, G. Howard and S. Ordway for editorial review, and D. McPherson and L. Manuntag for administrative assistance. This work was supported by grants (to L.M.) from the National Institutes of Health.

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Correspondence to Lennart Mucke.

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L.M. has been consulted by Merck and has received honoraria for lectures from Elan, Amgen and Pfizer.

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Palop, J., Chin, J. & Mucke, L. A network dysfunction perspective on neurodegenerative diseases. Nature 443, 768–773 (2006). https://doi.org/10.1038/nature05289

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