[Abstract Title]. - Society for Neuroscience

The Children‟s Foundation for Sleep and Neurobiology Research
SCOR 2P50HL65270
Title: Human apolipoprotein E4 transgenic mice subjected to chronic intermittent hypoxia
develop accelerated beta amyloid deposition in hippocampus and cortex
Authors: N. KAUSHAL, *D. GOZAL, V. RAMESH;
Dept Pediatrics, Kosiar Childrens Hosp Res. Inst., Louisville, KY
Abstract: The allele E4 of apolipoprotein E (ApoE4) is a well established genetic risk factor for
Alzheimer's disease, and has been associated with increased amyloid levels in brain. Although
epidemiological associations have emerged between ApoE4, AD, and sleep apnea, no studies
have specifically examined deposition patterns of beta amyloid in transgenic mice expressing
human ApoE4 in CNS exposed to a murine model of sleep apnea. ApoE4 transgenic mice (n=2)
and C57BL/6J WT mice (n=2) were chronically subjected to either intermittent hypoxia (IH;
cycling of 5.7% or 21% oxygen every 3 min) starting from 7.00 am to 7.00 pm (light period)
followed by room air (RA) until 7.00 am next day from age 7 months to 9.5 months.
Hippocampal and cortex sections were double stained with Neu-N and beta amyloid in both WT
and ApoE4 mice. Increased expression of beta amyloid was apparent in both hippocampus and
cortex in ApoE4 mice when compared to the control mice. In hippocampus, the increase in beta
amyloid appeared to be more prominent in the CA3 region. These preliminary results support the
hypothesis that chronic IH during sleep, as occurs in sleep apnea, not only imposes global
temporal effects on multiple physiological functions, but also enhances pathological changes in
neuronal structures, the latter further leading to accentuated sleep disturbances, and to
accelerated short-term memory and neurocognitive deficits.
Disclosures: N. Kaushal, None; D. Gozal , None; V. Ramesh, None.
Poster
243. Abeta Assembly and Deposition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 243.4/J10
Topic: C.01.b. Abeta assembly and deposition
Support: Alzheimer's Association
Title: Evidence for intraneuronal formation and accumulation of amyloid-beta oligomers in APP
transgenic mice