[Abstract Title]. - Society for Neuroscience

Abstract: Alzheimer‟s disease (AD) is characterized by extracellular Aβ peptide plaques and
intracellular hyperphosphorylated tau tangles. Extensive evidence from human AD patients and
transgenic mice support a central pathological role for soluble Aβ oligomers in AD. Aβ
oligomers are known to target neurons at synapses and may be responsible for synaptic failure
leading to neuritic cell death. Here we report at least two types of structurally distinct oligomers
exist as defined by their mutually exclusive reactivity with conformation dependent antibodies:
prefibrillar oligomers (PFOs) and fibrillar oligomers (FOs). Fibrillar oligomers react with a fibril
specific antibody, but are soluble (100,000 x G) and smaller than amyloid fibrils Here we
characterize the properties and toxicity of Aβ FOs. Aß FOs do not resemble amyloid fibrils but
rather appear as small (1 - 2 nm height) spherical or elongated particles. There are no obvious
morphological differences between FOs and PFOs although FOs may be slightly smaller than
PFOs. FOs are Thioflavin-T negative, unlike mature fibrils. Aβ PFOs selectively bind to neurons
at synapses, while FOs bind to neurons extensively at both synaptic and non-synaptic sites along
the entire dendritic processes. In vitro, Aβ FOs induce an apoptotic pathway involving
mitochondrial impairment in hippocampal and cortical neurons. Fibrils induce moderate cell
toxicity whereas monomers have no effect. Based on their similar tinctorial and immunological
properties, Aβ diffuse plaques may serve as reservoirs of FOs.
Disclosures: J.W. Wu , None; L. Breydo, None; Y.G. Kuznetsov, None; C.G. Glabe, CG is a
consultant for Kinexis, Inc, F. Consultant/Advisory Board.
Poster
243. Abeta Assembly and Deposition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 243.2/J8
Topic: C.01.b. Abeta assembly and deposition
Support: Grant of the Ministry of Education, Culture, Sports, Science, and Technology of Japan
Title: Staging for amyloid angiopathy in human aging
Authors: H. HATSUTA 1 , Y. SAITO 1 , R. SENGOKU 1 , T. ADACHI 1 , T. ARAI 2 , M.
SAWABE 2 , H. MORI 3 , *S. MURAYAMA 1 ;
1 Dept Neuropath, Tokyo Metropolitan Inst. of Gerontol, Tokyo 173-0015, Japan; 2 Dept
Pathology, Tokyo Metropolitan Geriatric Hosp., Tokyo 173-0015, Japan; 3 Dept Neurosci, Osaka
City Univ., Osaka, Japan
Abstract: PURPOSE: The present staging schemes for amyloid angiopathy (AA) in the aging
human brain are based on semi-quantitive evaluation of the severity of vascular changes. Thus,