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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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.
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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