Amyloid b Peptide – Mechanisms of Alzheimer’s Toxicity

 

Frank Heinrich, NIST Center for Neutron Research, NCNR, (Bldg. 235) Room E19, MS 8562, Tel: 301-975-4507, Fax: 301-921-9847, frank.heinrich@nist.gov, not a Sigma Xi member

 

Mathias Lösche (Mentor, NIST Center for Neutron Research, Carnegie Mellon University)

Duncan McGillivray (NIST Center for Neutron Research, Carnegie Mellon University)

Jim Hall (University of California, Irvine)

 

Category: Biology

 

Amyloid plaques associated with dead or damaged neurons are a characteristic property of neuronal cells suffering from Alzheimer’s disease. A major component of these plaques is the b-amyloid peptide (1-42), which is widely accepted to play a key role in the progress of Alzheimer’s disease. It has recently been shown that soluble oligomers are the primary toxic species of amyloid, although the actual mechanism of cell toxicity remains unclear [1]. Generally, two contrary hypotheses exist: either bA forms ion channels in the membrane [2] or bA leads to membrane thinning and disruption [3]. Neutron reflectivity is able to test both hypotheses by measuring bilayer thickness and completeness in presence of bA oligomers. The neutron experiments presented here reveal interactions of bA with artificial cell membranes using a well-characterized tethered lipid bilayer system. On incubation with bA oligomers POPC and DOPC lipid bilayers show thinning of the membrane by 1 to 3 Ĺ, and at high bA concentration destruction of the outer lipid leaflet, without any evidence of pore formation.

 

[1] R. Kayed et al., Science 300:486 (2003)

[2] S. Micelli et al., Biophys. J. 86:2231 (2004)

[3] R. Kayed et al., J. Biol. Chem. 279:46363 (2004)