[Abstract Title]. - Society for Neuroscience

Poster
243. Abeta Assembly and Deposition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 243.13/L3
Topic: C.01.b. Abeta assembly and deposition
Support: Alzheimer Association IIRG-06-27077
NIH/NIA Grant AG027973
NIH/NIA Grant AG31956
NIH/NIA Grant AG028794
Title: Regulatory role of Abca1 and brain lipoproteins in Aβ oligomerization and deposition -
comparative pathology in ABCA1ko and ApoA-Iko/ApoEko mice
Authors: R. KOLDAMOVA 1 , N. FITZ 1 , A. A. CRONICAN 1 , P. LEFTEROV 1 , *I. M.
LEFTEROV 2 ;
1 Envrn. & Occup. Hlth., Univ. Pittsburgh, Grad. Sch. of Publ. Hlth., Pittsburgh, PA; 2 Enviro &
Occup. Hlth., Univ. Pittsburgh, Grad. Sch. Pub, Pittsburgh, PA
Abstract: The ATP-binding cassette transporter (ABCA1) and apolipoproteins regulate
cholesterol and HDL formation. Recently, we and other groups demonstrated that APP
transgenic mice with engineered disruption of Abca1 (ABCA1 ko ) have an increased level of
amyloid plaques. In addition, Abca1ko mice have decreased levels of soluble apoA-I and apoE in
brain whereas the level of insoluble apolipoproteins is not changed. In APP mice with global
deletion of Abca1 the decrease of apoE and apoA-I is accompanied by an increase of insoluble
Amyloid beta (A[[Unsupported Character - Symbol Font ]]). Our most recent
experiments demonstrate that APP23 mice with one functional Abca1 allele (APP/Abca1 +/- ) have
cognitive deficits when compared to APP23 with intact Abca1 (APP/Abca1 wt ). We hypothesize
that Abca1-regulated generation of lipid-rich apoE, not the decreased levels of apoE and apoA-I,
is a critical mediator of A[[Unsupported Character - Symbol Font ]] aggregation. To
test this hypothesis we generated APP/PS1[[Unsupported Character - Symbol Font
]]E9 transgenic mice with global deletion of ApoE and ApoA-I genes (APP/ApoA-
I ko /ApoE ko ). In this study we have compared the amyloid deposition and cognitive decline in
APP/ApoA-I ko /ApoE ko to those in APP/Abca1 -/- and APP/Abca1 wt . The initial results of our
experiments show that the APP/Abca1 -/- mice have the highest level of amyloid deposition and
soluble A[[Unsupported Character - Symbol Font ]] oligomers. In contrast APP/ApoA-
I ko /ApoE ko double knockout mice have significantly less Thio-S positive plaques than
APP/Abca1 wt and APP/Abca1 -/- mice. Surprisingly, the level of soluble A[[Unsupported
Character - Symbol Font ]] oligomers in APP/ApoA-I ko /ApoE ko double knockout mice