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Alzheimer’s Disease and Neuronal Network Activity

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Abstract

The amyloid β-peptide theory of Alzheimer’s Disease has helped to advance our understanding of the disease tremendously. A new area of research focuses on the changes in neuronal network activity that take place and may contribute to the clinical and pathological picture of Alzheimer’s Disease. An apparent symptom of altered neuronal network activity in Alzheimer’s Disease is an increased frequency in epileptic seizures that is observed both in human patients and in mouse models of Alzheimer’s Disease. A root cause for altered network activity may be amyloid β itself by its ability to alter synaptic (glutamatergic) transmission and to impair the induction of long-term potentiation. It is on this aspect of Alzheimer’s Disease research that the current issue of NeuroMolecular Medicine will focus. Reviews will discuss the basic research and clinical aspects of the issue such as the effects of amyloid β on synaptic transmission and neuronal networks, as well as the changes in functional MRI activation patterns observed in early stages of Alzheimer’s Disease and the frequency and relevance of epileptic seizures in Alzheimer’s Disease patients.

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References

  • Bezprozvanny, I., & Mattson, M. P. (2008). Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends in Neurosciences, 31, 454–463.

    Article  CAS  PubMed  Google Scholar 

  • Chan, S. L., Mayne, M., Holden, C. P., Geiger, J. D., & Mattson, M. P. (2000). Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons. Journal of Biological Chemistry, 275, 18195–18200.

    Article  CAS  PubMed  Google Scholar 

  • Cheung, K. H., Shineman, D., Müller, M., Cárdenas, C., Mei, L., Yang, J., et al. (2008). Mechanism of Ca2+ disruption in Alzheimer’s disease by presenilin regulation of InsP3 receptor channel gating. Neuron, 58, 871–883.

    Article  CAS  PubMed  Google Scholar 

  • Forman, M. S., Mufson, E. J., Leurgans, S., Pratico, D., Joyce, S., Leight, S., et al. (2007). Cortical biochemistry in MCI and Alzheimer disease: Lack of correlation with clinical diagnosis. Neurology, 68, 757–763.

    Article  CAS  PubMed  Google Scholar 

  • Furukawa, K., Barger, S. W., Blalock, E. M., & Mattson, M. P. (1996). Activation of K+ channels and suppression of neuronal activity by secreted beta-amyloid-precursor protein. Nature, 379, 74–78.

    Article  CAS  PubMed  Google Scholar 

  • Guo, Q., Sopher, B. L., Furukawa, K., Pham, D. G., Robinson, N., Martin, G. M., et al. (1997). Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid beta-peptide: involvement of calcium and oxyradicals. Journal of Neuroscience, 17, 4212–4222.

    CAS  PubMed  Google Scholar 

  • Halagappa, V. K., Guo, Z., Pearson, M., Matsuoka, Y., Cutler, R. G., Laferla, F. M., et al. (2007). Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiology of Diseases, 26, 212–220.

    Article  CAS  Google Scholar 

  • Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., et al. (2003). APP processing and synaptic function. Neuron, 37, 925–937.

    Article  CAS  PubMed  Google Scholar 

  • Kuchibhotla, K. V., Goldman, S. T., Lattarulo, C. R., Wu, H. Y., Hyman, B. T., & Bacskai, B. J. (2008). Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron, 59, 214–225.

    Article  CAS  PubMed  Google Scholar 

  • Kumar-Singh, S., Dewachter, I., Moechars, D., Lübke, U., De Jonghe, C., Ceuterick, C., et al. (2000). Behavioral disturbances without amyloid deposits in mice overexpressing human amyloid precursor protein with Flemish (A692G) or Dutch (E693Q) mutation. Neurobiology of Diseases, 7, 9–22.

    Article  CAS  Google Scholar 

  • LaFerla, F. M., Tinkle, B. T., Bieberich, C. J., Haudenschild, C. C., & Jay, G. (1995). The Alzheimer’s A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice. Nature Genetics, 9, 21–30.

    Article  CAS  PubMed  Google Scholar 

  • Lalonde, R., Dumont, M., Staufenbiel, M., & Strazielle, C. (2005). Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen. Behavioural Brain Research, 157, 91–98.

    Article  CAS  PubMed  Google Scholar 

  • Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009). Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature, 457, 1128–1132.

    Article  PubMed  CAS  Google Scholar 

  • Loerch, P. M., Lu, T., Dakin, K. A., Vann, J. M., Isaacs, A., Geula, C., et al. (2008). Evolution of the aging brain transcriptome and synaptic regulation. PLoS One, 3, e3329.

    Article  PubMed  CAS  Google Scholar 

  • Lopez, J. R., Lyckman, A., Oddo, S., Laferla, F. M., Querfurth, H. W., & Shtifman, A. (2008). Increased intraneuronal resting [Ca2+] in adult Alzheimer’s disease mice. Journal of Neurochemistry, 105, 262–271.

    Article  CAS  PubMed  Google Scholar 

  • Markesbery, W. R., & Lovell, M. A. (2007). Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Archives of Neurology, 64, 954–956.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Mattson, M. P. (2004b). Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Annals of the New York Academy of Sciences, 1012, 37–50.

    Article  CAS  PubMed  Google Scholar 

  • Mattson, M. P., Cheng, B., Davis, D., Bryant, K., Lieberburg, I., & Rydel, R. E. (1992). beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. Journal of Neuroscience, 12, 376–389.

    CAS  PubMed  Google Scholar 

  • Mesulam, M. M. (2000). A plasticity-based theory of the pathogenesis of Alzheimer’s disease. Annals of the New York Academy of Sciences, 924, 42–52.

    Article  CAS  PubMed  Google Scholar 

  • Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., et al. (2008). Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease. Nature, 451, 720–724.

    Article  CAS  PubMed  Google Scholar 

  • Moechars, D., Lorent, K., & Van Leuven, F. (1999). Premature death in transgenic mice that overexpress a mutant amyloid precursor protein is preceded by severe neurodegeneration and apoptosis. Neuroscience, 91, 819–830.

    Article  CAS  PubMed  Google Scholar 

  • Nelson, O., Tu, H., Lei, T., Bentahir, M., de Strooper, B., & Bezprozvanny, I. (2007). Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. Journal of Clinical Investigation, 117, 1230–1239.

    Article  CAS  PubMed  Google Scholar 

  • Oddo, S., Caccamo, A., Cheng, D., Jouleh, B., Torp, R., & LaFerla, F. M. (2007). Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic mice. Journal of Neurochemistry, 102, 1053–1063.

    Article  CAS  PubMed  Google Scholar 

  • Oddo, S., Caccamo, A., Cheng, D., & Laferla, F. M. (2008a). Genetically altering Abeta distribution from the brain to the vasculature ameliorates tau pathology. Brain Pathology, 19, 421–430.

    Article  PubMed  CAS  Google Scholar 

  • Oddo, S., Caccamo, A., Kitazawa, M., Tseng, B. P., & LaFerla, F. M. (2003a). Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer’s disease. Neurobiology of Aging, 24, 1063–1070.

    Article  CAS  PubMed  Google Scholar 

  • Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., et al. (2003b). Triple-transgenic model of Alzheimer’s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron, 39, 409–421.

    Article  CAS  PubMed  Google Scholar 

  • Oddo, S., Caccamo, A., Tran, L., Lambert, M. P., Glabe, C. G., Klein, W. L., et al. (2006). Temporal profile of amyloid-beta (Abeta) oligomerization in an in vivo model of Alzheimer disease. A link between Abeta and tau pathology. Journal of Biological Chemistry, 281, 1599–1604.

    Article  CAS  PubMed  Google Scholar 

  • Oddo, S., Caccamo, A., Tseng, B., Cheng, D., Vasilevko, V., Cribbs, D. H., et al. (2008b). Blocking Abeta42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein: a mechanistic link between Abeta and tau pathology. Journal of Neuroscience, 28, 12163–12175.

    Article  CAS  PubMed  Google Scholar 

  • Palop, J. J., Chin, J., & Mucke, L. (2006). A network dysfunction perspective on neurodegenerative diseases. Nature, 443, 768–773.

    Article  CAS  PubMed  Google Scholar 

  • Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., 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.

    Article  CAS  PubMed  Google Scholar 

  • Palop, J. J., & Mucke, L. (2009). Epilepsy and cognitive impairments in Alzheimer disease. Archives of Neurology, 66, 435–440.

    Article  PubMed  Google Scholar 

  • Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., et al. (2008). Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nature Medicine, 14, 837–842.

    Article  CAS  PubMed  Google Scholar 

  • Sperling, R. A., Laviolette, P. S., O’Keefe, K., O’Brien, J., Rentz, D. M., Pihlajamaki, M., et al. (2009). Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron, 63, 178–188.

    Article  CAS  PubMed  Google Scholar 

  • Tu, H., Nelson, O., Bezprozvanny, A., Wang, Z., Lee, S. F., Hao, Y. H., et al. (2006). Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations. Cell, 126, 981–993.

    Article  CAS  PubMed  Google Scholar 

  • Zuccato, C., & Cattaneo, E. (2009). Brain-derived neurotrophic factor in neurodegenerative diseases. Nature Reviews: Neurology, 5, 311–322.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Intramural Research Program of the NIH, National Institute on Aging.

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Correspondence to Marc Gleichmann.

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Gleichmann, M., Mattson, M.P. Alzheimer’s Disease and Neuronal Network Activity. Neuromol Med 12, 44–47 (2010). https://doi.org/10.1007/s12017-009-8100-3

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  • DOI: https://doi.org/10.1007/s12017-009-8100-3

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