Poster Presentations: P3
aim of the current study was to compare levels of trace element Cu
(free copper and ceruloplasmin bound) in the serum of AD patients
(n¼44) and matched controls (n¼52). The objectives also included
assessing their relationship with cognitive and behavioural and psy-
chological functioning associated with dementia. Tools used were
Clinical Dementia Rating (CDR), Hindi Mental Status Examina-
tion (HMSE), Everyday Abilities scale for Indians (EASI) and
Neuropsychiatric Inventory (NPI) Results: Gender distribution
among AD group was 45% males and 55% females and in HC
group 52% males and 48% females. Mean age at assessment
for AD group was 68.32 69.74 years and for HC group was
65.75 67.6 years. No significant difference was found between
the two groups on age and gender. AD group obtained a lower
mean score as compared to the HC group on HMSE, and higher
on CDR, EASI & NPI indicating a poorer performance by AD
group. AD group was found to have lower levels of total serum
copper level (102.2 6 23.6 ug/dl) as compared to the control
group (115.9627.9 ug/dl). Also, Serum free copper level was
found to be lower in AD group (34.1611.2 ug/dl) as compared
to HC group (46.1614.8 ug/dl). No significant difference was
found between the two groups on Serum ceruloplasmin levels
Both total and free copper (but not ceruloplasmin per se) were
found to be lesser (p¼0.01 and p<0.001 respectively) in cases
than in controls. Conclusions: No appreciable difference could be
noted in levels of serum ceruloplasmin between the AD and healthy
control groups. However, significant decrease observed with copper
levels in the AD may account, in part, for decreased copper-depen-
dent biochemical activities such as cytochrome c oxidase required
for energy generation and superoxide dismutase (free radical scav-
enging enzyme) described in AD.
P3-097 SERUM INTERLEUKIN 1 ALPHA AND ALPHA 2
MACROGLOBULIN LEVELS IN PATIENTS WITH
EARLY- OR LATE-ONSET ALZHEIMER’S DISEASE
OR MILD COGNITIVE IMPAIRMENT
Irem L. Atasoy1, Erdinc Dursun1, Duygu Gezen-Ak1, Haşmet Hana
gası2,
Başar Bilgiç2, Ebba Lohmann2, Sibel Ertan1, Merve Alaylıo
glu1,
Om€ € 1, Ayşeg€ul G€und€uz1, G€uneş Kızıltan2,
€ ur S. Araz1, Burak Onal
H€ulya Apaydın1, Turgut Ulutin1, Hakan I. Gurvit2, Selma Yılmazer1,
1
Istanbul University, Cerrahpasa Faculty of Medicine, Istanbul, Turkey;
2
Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.
Contact e-mail: irem_aatasoy@yahoo.com
Background: Inflammatory processes are thought to be part of the
brain pathology in Alzheimer’s disease (AD). The interleukin 1
(IL-1) family consists of 11 cytokines that are key factors in regu-
lating inflammatory response to infections and sterile insults. IL-
1a is a membrane-anchored molecule and has autocrine signaling
mechanisms. Alpha-2 macroglobulin (a2M) is a unique molecule
which has ability to inhibit any protease, regardless of the active
catalytic site or the specificity of the protease. The aim of this
study is to compare the serum levels of IL-1a and a2M in early
onset AD (EOAD), late onset AD (LOAD) and mild cognitive
impairment (MCI) patients with age matched healthy controls.
Methods: Three groups of patients and two healthy control groups
which included control group for EOAD (n¼21), control group
for LOAD and MCI (n¼32), EOAD (age<65; n¼21), LOAD
P657
(age>65; n¼53) and MCI (age at MCI onset 60 to 78, n¼30)
were recruited. The dementia patients were clinically diagnosed
by DSM-IV criteria. Serum IL-1a and a2M levels determined
by ELISA. Results: The serum IL-1a levels significantly decreased
in the EOAD patients compared with their age-matched controls
(p<0.05). Similarly, the serum IL-1a levels of the LOAD patients
were significantly lower than their age-matched controls or the
MCI patients (p<0.05). The serum a2M levels of the EOAD
patients were similar to the LOAD or MCI patients. The serum
IL-1a levels of the EOAD patients were similar to the LOAD pa-
tients but were significantly lower than the MCI patients
(p<0.001). The correlation analysis noted that increased a2M
serum levels were correlated with increased age or age of onset.
A multiple regression analysis indicated that decreased serum
IL-1a levels were correlated with increased serum a2M levels
in the MCI patients. Conclusions: IL-1a was the only parameter
that significantly differed in the EOAD, LOAD patients from the
MCI patients or the healthy controls. IL-1a should be studied
more in both case control and longitudinal studies. Correlation
analysis of multiple biomarkers in different neurodegenerative dis-
orders might be more useful than determining the levels of a single
cytokine in a single disorder.
P3-098 SERUM URIC ACID, CEREBROSPINAL FLUID
MARKER OF ALZHEIMER’S DISEASE AND
COGNITION
Byoung Seok Ye1, Young H. Sohn1, Jee Hyun Ham1, Jae Jung Lee1,
Won Woo Lee1, Phil Hyu Lee1and the Alzheimer’s Disease Neuroimaging
Initiative1Yonsei University College of Medicine, Seoul, South Korea.
Contact e-mail: romel79@gmail.com
Background: Lower level of serum uric acid has detrimental effect
on the risk of dementia and cognitive impairment in the elderly.
However, underlying mechanism for the effect of uric acid has
not been elucidated. Methods: We investigated the association be-
tween serum uric acid and cerebrospinal fluid (CSF) level of bio-
markers including beta amyloid (Ab), tau, total tau (t-tau), and
phospho-tau (p-tau) using the database of the Alzheimer’s Disease
Neuroimaging Initiative (ADNI). According to serum uric acid
level, subjects were subgrouped into tertiles. Mixed-effect models
were used to evaluate the effect of serum uric acid on CSF bio-
markers and longitudinal cognitive decline. Results: Compared to
the middle uric acid tertile group, the lowest tertile group and the
highest tertile group had lower CSF Ab levels and higher tau and
p-tau levels, although statistical significance was reached only in
the lower tertile group. Both the lowest tertile and the highest tertile
groups had significantly higher CSF t-tau levels compared to the
middle tertile group. Serum uric acid showed detrimental effects
on longitudinal MMSE decline: in subjects with baseline MCI,
the lower tertile group had faster MMSE decline compared to the
middle tertile group (beta ¼ -1.13, p ¼ 0.002), while the higher ter-
tile group tended to have (beta ¼ -0.62, p ¼ 0.072); in subjects with
baseline dementia, both the lower tertile group (beta ¼ -2.84, p ¼
0.002) and the higher tertile group (beta ¼ -2.45, p ¼ 0.010) had
faster MMSE decline compared to the middle tertile group; but in
subjects with baseline normal cognition, the rate of decline was
comparable in the lower tertile (beta ¼ 0.16, p ¼ 0.533) and the
P658 Poster Presentations: P3
higher tertile (beta ¼ 0.07, p ¼0.724) groups compared to the mid-
dle tertile group. Conclusions: Our study showed that serum uric acid
is associated with CSF biomarkers of AD regardless of baseline
diagnosis and also associated with faster cognitive decline in
MCI and dementia patients. Both deficient and excessive serum
uric acid showed detrimental effects. These findings may provide
explanations for the association between serum uric acid and risk
of dementia in the elderly.
P3-099 THE CHANGE OF SERUM HOMOCYSTEINE (HCY)
AND HIGH SENSITIVITY C-REACTIVE PROTEIN
(HS-CRP) IN TIBETAN NATIONALITY PATIENTS
WITH ALZHEIMER’S DISEASE IN DIFFERENT
HIGH-ALTITUDE AREAS
Aiqin Zhu1, Yinglan Li1,2, Xin Zhong1, Guofeng Li1, Can Du1,
Xiangxin Guo1,2, Shizheng Wu1, 1Institute of Geriatric,Qinghai Provincial
Hospital, Xining, China; 2The University of Qinghai, Xining, China.
Contact e-mail: zhuaq@hotmail.com
Background: Tibetan nationality population was accounted for
48.4% in Qinghai-Tibet Plateau,which areas faced to many envi-
ronmental stresses, including chronic hypoxia, high altitude and
relative isolation from the outside world. To study Tibetan nation-
ality patients of Alzheimer’s disease(AD) at various high altitude
areas,serum Homocysteine (Hcy) and high-sensitivity C-reactive
protein (hs-CRP) was evaluated. Methods: We collected four groups
of high altitude areas in Qinghai-Tibet Plateau: Xining region (mid-
dle altitude at 2,260m), Yushu region (high altitude at 3,800m
above sea level): 25 Tibetan nationality patients of mild-to-moder-
ate AD at middle altitude and healthy Tibetan nationality elderly
from the same altitude;31 Tibetan nationality patients of mild-to-
moderate AD at high altitude and healthy Tibetan nationality
elderly from the same altitude. 112 people (50-87 years old) were
the half women and men. The patients were diagnosed according
to NINCDS /ADRDA and DSM-IV criteria as having the probable
AD. Every people was investigated with a questionnaire, which
including the basic information (age, race, cognize status, daily
life and social economic condition and social intercourse, smoking,
drinking, folic absorb, cholesterol and family history). Serum Hcy,
VitaminB12 and folic acid were measured by Fluorescence Polari-
zation Immunoassay. Serum hs-CRP, triglyceride (TG) and low
density lipoprotein cholesterol (LDL-c) were measured by TOSH-
IBA TBA-2000FR analyzer. Results: Compared to controls at same
high altitude, Hcy and hs-CRP were significantly increased in Ti-
betan nationality patients with AD (P<0.01). In AD groups,
HCY、TG、LDL-c and hs-CRP increased with altitude. On
contrast, folic acid between AD and control group were decreased
at high altitude compared those of middle altitude. Vitamin B12had
no change in the all of four groups. Multiple logistic regression
analysis showed the association between the nation, altitude, die-
tary habit, blood grease, folacins, Hcy, hs-CRP and patients with
AD at Plateau. Conclusions: Through study of correlation of Tibetan
patients with AD at various high altitudes and Hcy, hs-CRP, folic
acid,TG and LDL-C, we found that Tibetan AD patients had dietary
habits with more carnivorous dietary and high fat intake, less green
vegetable and fruit intake to result in inadequate intake of folic
acid. Therefore, Inflammation and vascular risk factors may
contribute to the development of Tibetan nationality AD in hypoxia
environment.
P3-100 THE DISTRIBUTION AND CLINICAL IMPACT OF
APOLIPOPROTEIN E4 AMONG PATIENTS WITH
SUBJECTIVE MEMORY IMPAIRMENT AND
EARLY MILD COGNITIVE IMPAIRMENT
Hanna Cho1,2, Young-Eun Kim2, Jong-Won Kim2, Duk L. Na3, Chang-
Seok Ki2, Sang Won Seo3, 1Gangnam Severance Hospital, Yonsei
University College of Medicine, Seoul, South Korea; 2Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;
3
Samsung Medical Center, Seoul, South Korea.
Contact e-mail: sangwonseo@empal.com
Background: Recent advances of Alzheimer’s disease (AD) bio-
markers have prompted more focus on the subjective memory im-
pairments (SMI) and early-stage amnestic mild cognitive
impairment (E-aMCI). These preclinical or prodromal stages of
AD is important to evaluate underlying mechanism for the future
development of AD, however, little is known about the distribu-
tion of the APOE e4 genotype, which is the most important ge-
netic variant associated with AD, and its clinical impact in
these groups. Therefore, the aim of this study was to investigate
the distribution of APOE e4 genotypes and to compare the neuro-
psychological results between APOE e4 carrier and non-carrier
across the full clinical AD spectrum including AD, late-aMCI
(L-aMCI), E-aMCI, SMI, and controls. Methods: We prospectively
recruited 713 patients with AD, 434 patients with L-aMCI, 215
patients with E-aMCI, and 575 patients with SMI at Samsung
Medical Center. All of the patients underwent a battery of neuro-
psychological tests and APOE4 genotyping. A large dataset from
8,260 individuals who took routine health examination from 1995
to 2002 at the Health Promotion Center of Samsung Medical Cen-
ter was used as controls. Results: The frequency of the APOE e4
allele showed an ordered fashion in the AD (30.8%), L-aMCI
(24.0%), E-aMCI (15.1%), SMI (11.7%), and control (9.1%)
groups. In the statistical comparisons of APOE e3/e3 vs. e3/e4 ge-
notype between diagnostic groups, relative to controls, all patients’
group had higher frequency of APOE e3/e4. Relative to SMI or E-
aMCI group, AD and L-aMCI groups had higher frequency of
APOE e3/e4 genotype. Relative to L-aMCI group, AD group had
higher frequency of APOE e3/e4 genotype. However there was
no significant difference between the E-aMCI and SMI groups. In
the neuropsychological test results between APOE e4 carrier and
non-carrier, SMI and E-aMCI group showed no significant differ-
ence. On the contrary, L-aMCI group showed memory impairment
in APOE e4 carrier, and AD group showed cognitive impairment in
the attention, language, visuospatial, memory, and frontal functions
in APOE e4 carrier. Conclusions: Our findings suggested that SMI
and E-aMCI had higher frequency of APOE4 genotype, but the
clinical impact of APOE4 were not prominent in two groups, unlike
L-aMCI and AD.