Poster Presentations: P2P394

on this topic is needed to understand underlying mechanisms as well as

predictors of individual improvements after specific non-pharmacological

treatments.

P2-373 THE ANTI-RHEUMATIC GOLD DRUG

AURANOFIN COULD BE BENEFICIAL IN

ALZHEIMER’S DISEASE BY INHIBITING

ASTROCYTE-MEDIATED

NEUROINFLAMMATION

Jocelyn Madeira, Colby Renschler, Nichole Gill, Andis Klegeris,

University of British Columbia, Kelowna, British Columbia, Canada.

Background:Alzheimer’s disease (AD) is characterized by chronic inflam-

mation in brain areas affected by the disease process, which may contribute

to the neuronal loss characteristic of AD. It is thought that by reducing this

inflammation, the neuronal loss observed in AD could be decreased. Astro-

cytes support neurons by regulating their external chemical environment,

but when activated by pathogenic stimuli, these cells can secrete pro-inflam-

matory and neurotoxic substances that contribute to neuroinflammation and

neuronal death. There are currently no effective therapeutic agents directed

at astrocyte neurotoxicity or neuroinflammation in general. Auranofin is

a potent anti-inflammatory drug which has been used in the treatment of

rheumatoid arthritis for many years and has been shown to inhibit several

inflammatory pathways such as those involving p38 mitogen activated pro-

tein kinases and thioredoxin reductase. However, a potential for auranofin to

reduce neuroinflammatory reactions has not been reported. Therefore, the

effectiveness of auranofin and several other gold-containing compounds

as inhibitors of astrocyte pro-inflammatory functions was investigated.

Methods: Effects of gold compounds on the following activation parame-

ters of interferon (IFN)-g stimulated humanU373-MG andU118-MG astro-

cytoma cells as well as primary human astrocytes were studied: i) mRNA

expression (RT-qPCR) of several inflammatory markers including interleu-

kin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1 and heme oxygen-

ase (HOX)-1; ii) pro-inflammatory cytokine secretion (ELISA); and iii)

toxicity towards SH-SY5Y neuroblastoma cells (MTTand LDH cell viabil-

ity assays). Results: In the low micromolar range (0.1-5 m M), auranofin

inhibited toxicity of stimulated astrocytoma and human primary astrocytes

towards SH-SY5Y neuroblastoma cells. Treating SH-SY5Y cells directly

with 1 m M auranofin protected neuronal cells from toxicity induced by su-

pernatants from stimulated astrocytes. 1 mM auranofin upregulated expres-

sion of HOX-1 in both stimulated and unstimulated astrocytes. It also

affected the secretion of pro-inflammatory cytokines. Several other gold-

based drugs and a gold salt had no effect in the above assays. Conclusions:

Auranofin may decrease toxicity of stimulated astrocytes towards neurons

by up-regulating expression of the protective enzyme HOX-1. As an effec-

tive inhibitor of neuroinflammatory reactions, auranofin should be tested in

animal models and clinically for its potential to slow neurodegeneration ob-

served in AD.

P2-374 EFFECTS OFANTI-TNF THERAPY ON AMYLOID

PATHOLOGYAND NEUROINFLAMMATION IN 12-

MONTH-OLD ARCAßTRANSGENIC MICE

Jordan McAfoose, Luka Kulic, Tobias Welt, Claudia Sp€ani,

Rebecca Derungs, Armanda Pfister, Roger Nitsch, Division of Psychiatry

Research, University of Zurich, Zurich, Switzerland.

Background: In 2008, Tobinick and colleagues demonstrated that Etaner-

cept anti-TNF therapy could be used for the treatment of AD. Although

this treatment approach has advanced to Phase II clinical trial the under-

lying therapeutic mechanisms remain unknown.Methods: To identify the

mechanisms we launched an AD mouse model study, in which we infused

Etanercept or vehicle control into the ventricles of arcAb mice over 28

days using ALZET osmotic minipumps; with an additional 15 non-treated

transgenic and wildtype mice as a further controls. All mice underwent

general health and neurological examination, as well as, cognitive assess-

ment before they were sacrificed for further biochemical and histological

analyses. Results: Our findings demonstrated a treatment dependent

improvement in cognitive performance in two hippocampus-dependent

cognitive tests. Biochemical analyses suggested that the improvement in

cognition was not associated with changes in soluble brain Abeta levels

but rather a decrease in Formic acid insoluble Abeta levels. Histological

analysis demonstrated a treatment-induced lowering of Abeta plaques

and an increased clearance of Abeta plaques towards the vasculature.S-

tainings against GFAP and Iba1 further demonstrated a reduction in astro-

cytosis with parallel elevations in microglia activation. Conclusions:

These findings suggest a neuroinflammatory and amyloid-lowering mech-

anism of anti-TNF therapy, in which Abeta is solubilized and cleared to-

wards the vasculature.

P2-375 MULTISTRATEGIC MEMORY TRAINING IN

ELDERS

Jiyoun Song1, Jung-Hae Youn2, Seolmin Kim3, Seung-Ho Ryu4, Maeng-

Je Cho5, Junyoung Lee1, 1Seoul National University Boramae Hospital,

Seoul, South Korea; 2Yongmoon Graduate School of Counseling

Psychology, Seoul, Korea, Seoul, South Korea; 3Konkuk University Medical

Center, Seoul, Korea, Seoul, South Korea; 4Konkuk University Hospital,

Seoul, South Korea; 5Seoul National University Hospital, Seoul, South

Korea.

Background:With the increase of the population of older people, the need

for effective training programs tomaintain or improve cognitive functions in

the elderly has been increasing. These cognitive enhancing training pro-

gramsmay contribute to the prevention of elderly cognitive decline by aging

and demented illness as well. This study aimed to examine the effectiveness

and the predictors of multistrategic memory training with the metamemory

concept on cognitive functions in the normal health elderly in Korea.

Methods: This multistrategic program used in this study was developed

by psychiatrists and psychologists in accordance with Korean situations.We

applied the training program to the community-dwelling elderly with sub-

jective memory complaints. We applied the training program to the commu-

nity-dwelling elderly with subjective memory complaints (n ¼ 107: No

cognitive impairment 95 and Mild Cognitive Impairment (MCI) 12).This

program consisted of 10 sessions and was administered once a week.We ex-

amined the effects of this memory training for verbal memory, visuospatial

memory, working memory, naming, and verbal fluency ability by repeated

ANOVA and we found predictors for cognitive improvement by linear re-

gression.Results: There were significant improvements inWord List Short-

term Delayed Cued Recall, Word list Long-term Delayed Free Recall, and

visuospatial delayed recall in intervention group compared to control group.

These improvements were still significant after adjusting for depression im-

provement and were predicted by MCI group. Conclusions: This study

shows that multistrategic memory training with the metamemory concept

may improve memory ability but don’t have transfer effect. These results

suggest the possibilities that cognitive training can delay dementia onset

in MCI patients.