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P3-103: Initial studies on the association between antemortem levels of cerebrospinal fluid β-secretase activity and post-mortem CERAD ratings of plaque densities in Alzheimer's disease

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P3-103: Initial studies on the association between antemortem levels of cerebrospinal fluid β-secretase activity and post-mortem CERAD ratings of plaque densities in Alzheimer's disease
  Mean (SD) Hippocampal Structure Measures L  R Hipp Volume (mm3) GroupCDR 0CDR 0.5Baseline3546 (1205)3554 (1126)Slope (peryear)-41 (74)-120 (66) L  R Hipp CA1 (mm) CDR0CDR0.5-0.041 (0.30)-0.45 (0.39)-0.014 (0.040)-0.073 (0.043)L  R Hipp Subiculum (mm) CDR0CDR0.50.029 (0.17)-0.21 (0.23)-0.011 (0.022)-0.023 (0.017)L  R Hipp Remainder (mm) CDR0CDR0.50.105 (0.23)0.09 (0.38)-0.020 (0.036)-0.039 (0.034) Mean (SD) CSF Measures CSF tau CDR 0CDR 0.5347 (209)447 (211) CSF p-tau 181 CDR0CDR0.561 (31)69 (25)CSF A  42 CDR0CDR0.5563 (195)475 (203) P3-103INITIAL STUDIES ON THE ASSOCIATIONBETWEEN ANTEMORTEM LEVELS OFCEREBROSPINAL FLUID  -SECRETASEACTIVITY AND POST-MORTEM CERADRATINGS OF PLAQUE DENSITIES INALZHEIMER’S DISEASEJonathan H. Williams , Catharine Joachim, David Smith,Gordon K. Wilcock, Oxford University, Oxford, United Kingdom.Contact e-mail:  Jonathan.Williams@dpag.ox.ac.uk  Background: In Alzheimer’s disease (AD) the brain shows high densitiesof plaques containing beta-amyloid (A  ). Despite this, CSF levels of A  peptides are low in AD. The activity of  -amyloid converting enzyme(BACE) appears rate-limiting in the production of APP fragments (sAPP  and A  ). Although post-mortem BACE levels and activity in brain appearhigher in AD, ante-mortem CSF BACE activity levels have been reportedas elevated or unchanged in AD. We aimed to further examine the rela-tionship between ante-mortem CSF BACE activity and APP processingwith post mortem plaque and tangle densities. Methods: We obtained CSFby lumbar puncture from 17 AD patients, for whom post mortem plaqueand tangle ratings showed CERAD ‘Probable’ or ‘Definite’ AD, and 27cognitively healthy controls of similar age (post mortems in 6 confirmed‘Normal brain’). Results: Mean CSF BACE activity was significantlylower in AD patients (77% of control activity, p  0.01). CSF sAPP  ,A  1-40 and A  1-42 levels were also lower in AD patients (78%, 73% and45% of control levels, p  0.01, p  0.001, p  0.001, respectively). CSFsAPP  ,A  1-40 and A  1-42 levels all related directly to CSF BACE activity(all p  0.005). The altered CSF A   levels in AD patients remained signif-icant if we covaried BACE activity. CSF BACE activity, A  1-40 andA  1-42 levels all related inversely to CERAD ratings of plaques (p  0.015,p  0.04, p  0.007, respectively). Conclusions: The reduced CSF BACEactivity in AD patients appears consistent with the lower CSF A   levels.However whether this directly reflects reduced APP catabolism remainsuncertain. The inverse dependence of CERAD plaque ratings on both CSFBACE activity and A   levels raises the alternative possibility that acommon mechanism, such as sequestration by plaques, lowers both. P3-104CD44 (CELL SURFACE MARKERS) EXPRESSIONEVALUATION IN ADJUVANT-INDUCEDARTHRITIC MODEL OF RATSShiraz Ahmed , Maheen Hassan, The Aga Khan University, Karachi,Pakistan. Contact e-mail: shiraz.ahmed@aku.edu Background: Rheumatoid arthritis is an inflammatory disorder that causesthe immune system to attack the joints and synovial tissue. The process of inflammation is triggered by upregulation of CD44 inflammatory cellsespecially during the progression of inflammation in rheumatoid arthritis.CD44 protein is cell-surface glycoprotein involved in cell-cell interactions,cell adhesion and are expressed in variety of connective tissues and he-matopoietic cells. This cell surface receptor has been reported to playsignificant role in advancement of arthritis by directing leukocyte traffic tothe inflammatory site. In addition, interaction between CD44 and extracel-lular hyaluronan has been reported to be involved in variety of physiolog-ical and pathological processes including T-cell activation and leukocyteextravasations at the inflammatory site. Methods: In this study, the effectof anti-arthritic agents on the expression of CD44 markers and the effectsof test compounds in reducing pain and inflammation has been investigatedand for this purpose we have used adjuvant induced arthritis model of painin rats. Immunohistochemistry for CD44 cell surface markers was doneusing monoclonal anti-CD44 antibodies. Results: Our results demonstratesignificant increase in the CD44 expression in the brain samples of thearthritic rats. In contrast, the animals treated with indomethacine or testcompound OS2 showed marked reduction in the expression of this markerin the brain samples. However, when the treated animals were comparedwith each other, the arthritic rats administered with OS2 showed futherreduction in the expression of CD44 marker which was comparable to thenon-arthritic control group. The advancement in the disease was scruti-nized by assessing body weight and paw volume. The arthritic rats treatedwith indomethacine and OS2 not only inhibited the macroscopic changessuch as erythema and swelling of limbs, but also exhibited marked atten-uation of the increase in paw volume produced as a result of arthritisinduction. There was also a minor but insignificant reduction in the bodyweights of OS2 treated arthritic rats however it was recovered in the end. Conclusions: Based on these results, we suggest that OS2 is not onlyanti-inflammatory but also control the underlying mechanism of the in-flammatory processes associated with arthritis. P3-105LOW EPISODIC MEMORY PERFORMANCE ISRELATED TO HIGH PET PIB LEVELS INASYMPTOMATIC CONTROL SUBJECTSOve Almkvist , Anton Forsberg, Agneta Nordberg, Karolinska Institutet,Stockholm, Sweden. Contact e-mail: ove.almkvist@neurotec.ki.se Background: PET PIB measurement is thought to mirror the amount of amyloid in the brain, which is a hallmark of Alzheimer’s disease (AD).Recent research has shown that PIB values are clearly higher, althoughrelatively stable, in AD vs. controls. The question is when do PIB valuesincrease? Methods: 60 subjects were divided into three groups after acomprehensive clinical examination including anamnesis; reports on symp-toms from a close informant; medical history; physical status; analyses of blood, urine and CSF; MRI; and assessment of cognitive function as wellas PET PIB measurement. A follow-up examination was performed about2.5 years later to verify the clinical diagnosis of AD (n  37), MCI pa-tients(n  14) as well as healthy controls (n  9). Results: Within-groupregression analyses demonstrated significantly increasing PIB values inmost brain regions in relation to decreasing episodic memory results incontrols. In contrast, PIB values in AD patients were invariant on a highlevel and episodic memory was decreasing when disease advanced. ForMCI patients, an association existed between higher PI and poorer mem-ory, although it did not reach statistical significance. In other cognitivedomains, no significant covariance were seen in relation to PIB in anygroup. Conclusions: Within controls, high PIB reflected low episodicmemory performance that may indicate a very early preclinical phase of ADdevelopment. P3-106SCREENINGFORMEMORYPROBLEMSINALARGEGROUPSETTINGJ.W.Ashford ,EmilyGere,DerylWicks,SaminaGul,RajKumarSharma, Stanford/VAAgingClinicalResearchCenter,Palo Alto, CA, USA. Contact e-mail: washford@medafile.com T549 PosterPresentationsP3:
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