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December 22, 2005
Rehabilitating Amyloid beta: Abeta is an essential synaptic protein, not neurotoxic junk, Neuron study suggests
While adherent to the phrasing of the amyloid dogma (AK: otherwise how this report would be favorable reviewed and published in Neuron?) the study by Cirrito et al. says amyloid beta is a functional activity-dependent synaptic protein. What a Holiday gift for Alzheimer's field members combating amyloid cascade hypothesis dogma. The abstract of the study and recent related essential reading citations follow:
"Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis. Abeta aggregation is concentration dependent and brain region specific. Utilizing in vivo microdialysis concurrently with field potential recordings, we demonstrate that Abeta levels in the brain interstitial fluid are dynamically and directly influenced by synaptic activity on a timescale of minutes to hours. Using an acute brain slice model, we show that the rapid effects of synaptic activity on Abeta levels are primarily related to synaptic vesicle exocytosis. These results suggest that synaptic activity may modulate a neurodegenerative disease process, in this case by influencing Abeta metabolism and ultimately region-specific Abeta deposition. The findings also have important implications for treatment development."
Source: Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtzman DM. Synaptic Activity Regulates Interstitial Fluid Amyloid-beta Levels In Vivo. Neuron. 2005 Dec 22;48(6):913-922 [PubMed Abstract and FullText link] [Associated Neuron Commentary]
Essential related reading:
Koudinov A and Koudinova N. Amyloid b protein restores hippocampal long term potentiation: a central role for cholesterol? Neurobiology of Lipids 1, 8 (2003). Published online September 15, 2003. [Free FullText] [AlzForum hypothesis]
Koudinov AR, Berezov TT. Alzheimer's amyloid-beta (A beta) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiol Exp (Wars). 2004;64(1):71-9 2 [Free .PDF FullText]
Grimm MOW, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T. Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nature Cell Biology (9 October 2005) ePub ahead of print. [Abstract Link and SFN presentation][AlzForum Discussion]
"Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis. Abeta aggregation is concentration dependent and brain region specific. Utilizing in vivo microdialysis concurrently with field potential recordings, we demonstrate that Abeta levels in the brain interstitial fluid are dynamically and directly influenced by synaptic activity on a timescale of minutes to hours. Using an acute brain slice model, we show that the rapid effects of synaptic activity on Abeta levels are primarily related to synaptic vesicle exocytosis. These results suggest that synaptic activity may modulate a neurodegenerative disease process, in this case by influencing Abeta metabolism and ultimately region-specific Abeta deposition. The findings also have important implications for treatment development."
Source: Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR, May PC, Schoepp DD, Paul SM, Mennerick S, Holtzman DM. Synaptic Activity Regulates Interstitial Fluid Amyloid-beta Levels In Vivo. Neuron. 2005 Dec 22;48(6):913-922 [PubMed Abstract and FullText link] [Associated Neuron Commentary]
Essential related reading:
Koudinov A and Koudinova N. Amyloid b protein restores hippocampal long term potentiation: a central role for cholesterol? Neurobiology of Lipids 1, 8 (2003). Published online September 15, 2003. [Free FullText] [AlzForum hypothesis]
Koudinov AR, Berezov TT. Alzheimer's amyloid-beta (A beta) is an essential synaptic protein, not neurotoxic junk. Acta Neurobiol Exp (Wars). 2004;64(1):71-9 2 [Free .PDF FullText]
Grimm MOW, Grimm HS, Patzold AJ, Zinser EG, Halonen R, Duering M, Tschape JA, De Strooper B, Muller U, Shen J, Hartmann T. Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilin. Nature Cell Biology (9 October 2005) ePub ahead of print. [Abstract Link and SFN presentation][AlzForum Discussion]
posted by Dr. Koudinov @ 22.12.05
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