[Abstract Title]. - Society for Neuroscience

and/or intracellular.
Recently it has been proposed that a hierarchical assembly mechanism in which amyloidogenic
proteins begin with a random coil structure, are then misfolded and next aggregate into spherical
oligomers. The spherical oligomers can then further aggregate into chain-like protofibrils and/or
annular protofibrils, and finally form the fibrils present in amyloid. Many research groups are
using a variety of techniques to detect and probe these aggregates, especially the soluble forms of
Aβ recently described as the most toxic species implicated with synapse loss and synaptic
function impairment in the early stages of the disease.
In this study, we used a combination of sequence specific Aβ antibodies and novel conformation
antibodies against different amyloid species, specifically anti-oligomers, anti-fibrils and antiannular
protofibrils to investigate the location and conformation of each amyloid species in
transgenic mouse models. Immunohistochemistry, Western Blot and immunoprecipitation were
used to analyze and characterize the different amyloid species in these animals at different ages.
We found the presence of both intracellular and extracellular Aβ oligomers, while the
extracellular oligomers were similar to the ones detected in AD brains and located where
amyloid plaques are. Intracellular and membrane associated oligomers were also detected, and
are being analyzed. These results are important to understand the dynamic changes of Aβ
deposits in both location and conformation and their role in the progression of the disease.
Disclosures: C.A. Lasagna-Reeves , None; C. Soto, None; R. Kayed, None.
Poster
243. Abeta Assembly and Deposition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 243.8/K2
Topic: C.01.b. Abeta assembly and deposition
Support: NCCR Zurich Neural plasticity and repair
SNF Grant 310000-117806
Title: Reduced Reelin-dependent signaling affects amyloid-β plaque formation in-vivo
Authors: *I. KNUESEL, S. KOCHERHANS, F. CRESTANI, C. SIDLER, J.-M. FRITSCHY;
Inst. of Pharmacol. and Toxicology, Univ. of Zurich, Zurich, Switzerland
Abstract: Besides the control of cortical lamination during neurodevelopment, several recent
findings suggest novel roles for the glycoprotein Reelin and its receptors in the pathogenesis of
Alzheimer‟s disease (AD). The highly conserved protein is a pivotal synaptic regulator which