SAGE KE Bulletin Board

Toxic forms of the amyloid beta-protein (Abeta): Abeta-oligomers and fibrillar Abeta

4 November 2004

Dietmar R. Thal

Evidence has been shown that Abeta oligomeres alter synaptic structures and modulate glutamate receptors (Cui, et al. 2004; Lacor, et al. 2004). Monomeric Abeta does not seem to be that toxic. This hypothesis is supported by the finding that synaptic alterations in APP-transgenic mouse brain are located only near plaques containing fibrillary amyloid (Tsai et al. 2004). In so doing, both observations clearly point out that monomeric Abeta may not be the toxic agent but oligomeric and fibrillar forms of Abeta are toxic. Whether Abeta plaques itself are toxic or whether oligomeric Abeta in their vicinity is the critical agent is not clear. However, evidence has been shown that synaptic and neuronal alterations already arise before Abeta-deposition takes place (Wu et al. 2004) indicating that Abeta-oligomeres may play the key role in Abeta-toxicity. References Cui, C., E.K.Dimitriadis, et al. (2004). "Modulation of glutamate receptors by soluble oligomers of amyloid beta peptides." 2004 Abstract Viewer/Itinerary Planner: Program No. 218.18. Lacor, P. N., M. C. Buniel, et al. (2004). "ADDLs (Abeta oligomers) alter structure and function of synaptic spines." 2004 Abstract Viewer/Itinerary Planner.: Program No. 218.3. Tsai, J., J. Grutzendler, et al. (2004). "Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches." Nat Neurosci 7(11): 1181-3. Wu, C. C., F. Chawla, et al. (2004). "Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: digital morphometric analyses." Proc Natl Acad Sci U S A 101(18): 7141-6.

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