Differential expression of mRNAs detected by cDNA microarrays in Alzheimer's disease

Poster Presentation:

Sl62

APOE AND LIPID PROFILES IN PROBABLE AND POSSIBLE AD PATIENTS VERSUS CONTROLS IN BOGOTA (COLOMBIA).

BENEFITS OF DONEPEZIL IN THE TREATMENT OF BEHAVIORAL PROBLEMS IN MODERATE TO SEVERE ALZHEIMER’S DISEASE Orlando Jnnr

Hwkrr.

Vmcmwr, Cnnndu:

Rrpatrration BC Conada:

Bnmo

Ed Whalen,

pfixr

Vellas,

Gm

Hosp.

Serge Gnuthier, Torrloww

Pharmaceuticals

Univ

DUM’ Park Mf,CiI/ Arad

Group.

Australia; Ctrfor

Foti,

Study on Aging.

Ctr. Alhuyuerqu~. Nw

Dean

NM;

Univ

Hasp,

Verdun,

Ponni

PQ

Suhhiuh.

York, NY

Bogota Patricia lnst

Bogotrr

EXPRESSION OF MRNAS DETECTED [7351 DIFFERENTIAL CDNA MICROARRAYS IN ALZHEIMER’S DISEASE

Ton-es.

Univ Javeriana,

Colombia; Montanes,

Nncional

Sulud,

Controlled clinical trial\ of donepezil have demonstrated short- and long-term benefits on cognitive and functional domain? in patients with mild to moderate Alrheimer’s disease (AD). Typically, however, as the diseaw progreaaes through the moderate to severe stage, a variety of behavioral problems mamfest. As part of this 24.week, double-blind, placebo-controlled trial in patient\ with moderate to severe AD. the effect of donepezil on neuropsychiatric rymptoms wa\ investigated. Patients from 32 centers were randomized to either donepuil (5 mglday for 28 days followed by 10 mglday as per the clinician‘s judgement, n= 144) or placebo (n= 147). Outcome rneasure~ mcluded the 12.item Neuropaychiatric Inventory (NPI). Safety assessments mcluded momtormg treatment-emergent adverse events (AEa). Baseline demographic)I were similar between the treatment groups (mean age: 73.6 years, range: 4X-92: mean sMMSE scores: Il.8 f 3.6 and 12.2 -t 3.X for donepezil and placebo groups, rerpectively). Improvements from baseline NPI 12.item total scores were observed at all visits for donepwil. compared with placebo, reaching statistical significance at Weeks 4 and 24 (p
Clinical Research III

Bogota

Diana

Arango,

Univ National

de S&d, Colombin:

Bogota Sandra

Bogota

Colombiu:

Lab of Molecular de Colombia, Colombia;

Carlos

Bogota

Angela

Suescun, Martinr

Cam,

Genetics-UIA, Colombia;

Buhamon, Jmqrrier,

Hasp sari Ignacio, Antwerp Alberta

hsiruto

Belgium: Shinchi.

Nacionul

Inst Nucional

dr

de Salad,

Colombia

Besides being an important genetic susceptibility factor for AlTheimer’r disease (AD), APOE E4 was related to hypertension, coronary disease and dyslipidemia\, both in clinical and population studies. The influence of vascular risk factors on the expresrion of AD is currently a topic of interest and APOE E4 might be pati of the bridging factors between AD and vascular dementia. Also, home authors suggested that the susceptibility to AD related to APOE status might be modulated by dietary cholesterol intake, which might lead to preventive and therapeutic approaches. Fat intake is known to be high m Colombia according to traditional dietary habits. The association of the APOE E4 allele with Alzheimer‘s d&use in Colombia xvi,\ confirmed in a previous study by our team. We meant to assess if the APOE E4 allele was associated with hypertension, high cholesterol and triglyceride (TG) levels in Colombian cases and controls in a pilot clinical arudy. We studied 32 AD patients (IX with probable and I4 with possible AD) in mild to moderate stages of disease, previously diagnosed by clinical consensus according to NINCDS-ADRDA critena and 53 matched controls; all subjects were genotyped for APOE and clinically screened for hypertension, cardio-vascular diseases and Hachinski scale. Their dietary intake was evaluated through a Spanish version of the NSI checklist and a standardized food frequency questionnaire; their plasma lipid profile (total choleaterol. HDL cholesterol. LDL cholesterol and TG) was obtained by enzymatic methods. We did not find an aswciation between bearing at least an APOE E4 allele and hypertension. We found no differences on total cholesterol, HDL cholesterol or LDL cholesterol, between AD patients versus controls and between APOE E4 bearers versus no bearers. APOE E4 bearers had a slightly higher TG level but the difference was not statistically significant and this result might be due to a sample effect as 2 wbjects with the APOE E4E4 genotype presented with severe hypertriglyceridemia. Further studies in Colombia on a population basis , controlling for family history , food habit+, and life-style will allow to further assess the relationship between the APOE E4 allele and vaxular risk factors.

BY ASSESSMENT OF EMOTIONAL ALZHEIMER’S DISEASE

To elucidate the genetic mechanisms of Alzheimera diseaw (AD), we investlgared the regional differences in gene expression of AD bran by using cDNA microxrayr. Microarrays allow a quantitative parallel analysis of expression of more than 8000 genes wlthm a sample at the rame time and under identical conditions. Gene expresrion in the hippocampus where neurofibrillary tangles (NFT) were detected histopathologically was compared with the par&al cortex from the same patient where neither NFT nor neuronal 10% wab detected. To avoid the physiological difference of gene exprasion, we also compared the differential gene expression between both areas of the non-AD control bran where NFT and neuronal loss were rarely detected. The result\ demonwated that approximately 200 genes were vgnificantly up-regulated and about IO0 genes were significantly down-regulated in the hippocampus compared wth the parietal cortex of the AD brain. Whereas, approximately 100 gene< were significantly up-regulated and about 100 genes were significantly down-regulated m the hippocampu~ compared with the parietal cortex of the non-AD control brain. Among of them, for example, calcineurin A@ showed
MEMORY IN PATIENTS

WITH

Background Emotionally mzaningtul events as a general rule are more eaailq remembered than event\ devoid of emotional content. One explanation for this is that the amygdala is activated. Given the pathological alterations seen in the amygdala of AD patients, some kind of emotion processing impairment is to be expected in these patients. Indeed, some authors have demonstrated a defective processing of emotional cues in AD patients, m&ding an impairment m the processing of facial expressions. On the other hand, Ikeda et al. (19Y9) showed that AD patient.\ living in Kobe when the earthquake happened were able to remembered this experience with a strong emotional content. Objective In this study we examined whether AD patients can benefit from the emotional content of visual stimuli in a picture recognition test. Method\ eighteen patients with Allheimer disease and 20 normal controls matched for age and year\ of education, were studied. Sixteen pictures (with varying emotional contents) were presented to each participant. Thirty minutes later, R recognition te\t was applied with the target-picturea mixed among 34 others of similar contents. The wbjects were instructed to rate them as pleasant. unpleasant or indifferent. Result? Alzheimer’s wbjects were as able as the controls to rate pictures according to their content. Emotional content enhanced recognition of pictures in normal wbjccts, whereaa for the Alzheimer’a subjects the emotional significance attached to the pictures was of no benefit to enhance recognition Conclusiona Our data are in disagreement with those of Ikeda.). These authors invatigated the memory of AD for the Kobe earthquake AD patients remembered the earthquake more than a neutral posterior event. It is important to note that the emotionally charged pictures used in this investigation were not a personal experience of each subject. It is possible that in AD subjects there is a difference between personally lived experiences and situations witnessed without a personal participation. Another hypothesis to explain this difference could be the uneven intensity of emotional content’s in these two experiments. More studies are needed to clarify these hypotheses