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Poster P2:: Monday Posters interest of the biomarkers for the prediction of conversion of MCI to AD will be determined by a longitudinal study. P2-134

AGE AND APOLIPOPROTEIN E*4 EFFECTS ON CEREBROSPINAL FLUID A〉42 IN COGNITIVELY NORMAL ADULTS

Elaine R. Peskind1,2, Gail Li1,2, Jane Shofer1, Joseph Quinn3,4, Jeffrey Kaye3, Christopher M. Clark5, Martin Farlow6, Charles DeCarli7, Murray A. Raskind1,2, Gerard D. Schellenberg1,2, Virginia M-Y Lee5, Douglas Galasko8,9, 1VA Puget Sound Health Care System, Seattle, WA, USA; 2University of Washington School of Medicine, Seattle, WA, USA; 3 Oregon Health and Science University, Portland, OR, USA; 4Portland VA Medical Center, Portland, OR, USA; 5University of Pennsylvania, Philadelphia, PA, USA; 6Indiana University School of Medicine, Indianapolis, IN, USA; 7University of California at Davis, Sacramento, CA, USA; 8University of California at San Diego, San Diego, CA, USA; 9 VA San Diego Health Care System, San Diego, CA, USA. Contact email: [email protected] Background: Cerebrospinal fluid (CSF) beta amyloid 42 (A␤42) concentrations are decreased in Alzheimer’s disease (AD), possibly reflecting precipitation of A␤42 in amyloid plaques in brain parenchyma. Objective: Because amyloid deposition likely begins years before the clinical expression of dementia in AD, this CSF A␤42 decrease may be detectable before clinical dementia is expressed. Normal aging and presence of the apolipoprotein E (APOE)*4 allele are the most important known risk factors for AD. Methods: Here we estimated the interactive effects of normal aging and presence of the APOE*4 allele on CSF A␤42 in cognitively normal adults across the lifespan. CSF was collected in the morning after an overnight fast using Sprotte 24g atraumatic spinal needles. Results: CSF A␤42 and A␤40 concentrations were measured in the 10th ml of CSF collected by sandwich ELISA. APOE genotype was determined by a restriction digest method. Subjects were 184 cognitively normal community volunteers aged 21-88. CSF A␤42 but not A␤40 decreased significantly with age. There was a sharp decrease in CSF A␤42 beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A␤42 was significantly and substantially greater in subjects with the APOE*4 allele compared to those without the APOE*4 allele. Conclusions: These CSF A␤42 findings are consistent with acceleration by the APOE*4 allele of pathogenic A␤42 brain deposition starting in later middle age in cognitively normal persons, and suggest that CSF A␤42 may have utility as a biomarker for AD pathobiology in cognitively normal older persons and those with mild cognitive impairment. P2-135

EXCESS OF NON CERULOPLASMIN SERUM COPPER IN ALZHEIMER DISEASE CORRELATES WITH MMSE, CSF BETA-AMYLOID AND H-TAU

Rosanna Squitti1, Giulia Barbati1, Luisa Rossi2, Mariacarla Ventriglia1, Gloria Dal Forno3, Simona Cesaretti1, Filomena Moffa1, Emanuele Cassetta1, Lilia Calabrese4, Paolo Maria Rossini1, 1AFaROspedale Fatebenefratelli, Rome, Italy; 2Dept. Biology, Tor Vergata University, Rome, Italy; 3‘Campus Biomedico’ University, Rome, Italy; 4 Dept. Biochem. Sci. “La Sapienza” University, Rome, Italy. Contact e-mail: [email protected] Background: Neurodegeneration in Alzheimer disease (AD) may depend on copper-mediated mechanisms. Previous studies described the increase in AD of a serum copper fraction unrelated to ceruloplasmin that could cross the blood brain barrier. Objective: To assess if serum copper in AD correlates with cognitive scores, beta-amyloid (␤-amyloid) and other CSF markers of neurodegeneration. Methods: We studied serum copper, ceruloplasmin, total peroxides and antioxidant levels (TRAP), and CSF copper, ␤-amyloid, h-tau and P-tau in 28 patients with AD and 25 healthy controls, in relation to clinical status. Results: Serum copper (p ⬍ 0.0001), peroxides (p ⫽ 0.002), a copper fraction unexplained by ceruloplasmin (p ⬍ 0.0001), and CSF h-tau (p ⫽ 0.001) were increased in AD, while serum

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TRAP (p ⫽ 0.03) and CSF ␤-amyloid were decreased (p ⬍ 0.0001). CSF markers of AD correlated with serum copper-variables. CSF copper was partially dependent on the serum copper fraction unexplained by ceruloplasmin (t ⫽ 2.2, p ⫽ 0.04). CSF ␤-amyloid seemed related to serum copper (r ⫽ ⫺0.46; p ⫽ 0.002). MMSE scores correlated positively with ␤-amyloid (r⫽ 0.46, p⫽ 0.002) and inversely with copper unexplained by ceruloplasmin (r⫽ ⫺0.45, p⫽ 0.003). Conclusions: Our results confirm the existence of changes in copper components distribution, particularly the copper fraction unexplained by ceruloplasmin. Abnormalities in copper and ␤-amyloid metabolism could represent a key in understanding the role of metals in the functional loss of AD. P2-136

DIFFERENTIAL CSF BUTYRYLCHOLINESTERASE LEVELS IN ALZHEIMER’S DISEASE PATIENTS WITH THE APOE ⌭4 ALLELE, IN RELATION TO COGNITIVE FUNCTION AND CEREBRAL GLUCOSE METABOLISM

Taher Darreh-Shori1, Steven Brimijoin2, Ahmadul Kadir1, Ove Almkvist1, Agneta Nordberg1, 1Karolinska Institutet, Stockholm, Sweden; 2Department of Molecular Pharmacology, Mayo Clinic, Rochester, USA. Contact e-mail: [email protected] Background: The risk of developing Alzheimer’s disease (AD) increases in subjects carrying the ⑀4 allele of the apolipoprotein E gene (ApoE) and a certain genetic variant of butyrylcholinesterase (BuChE) with reduced circulating molecules. Both variables seem to be predictive of a poorer response to cholinesterase inhibitors (ChEIs). Cortical expression of BuChE is increased in AD brain. Objective: In this study we investigated whether the BuChE levels in CSF differed between AD patients with or without ApoE ⑀4 allele and whether such differences were related to the cognition and the cerebral glucose metabolism (CMRglc) in AD patients prior to commencing treatment with ChEIs. Methods: Baseline CSF samples from a total of eighty mild AD patients who had participated in three previous ChEIs studies (rivastigmine (n⫽11), donepezil (n⫽54) and galantamine (n⫽15)) were included. Results: Gender and ApoE ⑀4 genotype, but not age were the main factors that were related to the levels of BuChE in the CSF of patients. The BuChE activity was 23⫾8% higher in men (n⫽ 40) than in women (p⬍0.03, n⫽40) and 40-60% higher in the ApoE ⑀4 non-carrier than in the AD patients carrying one or two ⑀4 alleles (all p⬍0.0004). The global cognitive function of the AD patients, assessed by MMSE was significantly higher in AD patients with a high to moderate CSF BuChE compared to those with a low BuChE level. Significant correlations were observed between the CSF BuChE level and MMSE, ADAS-Cog and cortical CMRglc. Conclusions: A low level of BuChE in CSF may be predictive of a higher degree of neurodegeneration in AD brain, most likely due to a more extended incorporation of BuChE in neuritic plaques. P2-137

ANALYSIS OF LOW-ABUNDANT PROTEINS IN BODY FLUIDS

Katja Hanisch, Ralf Hoffmann, Bianalytics, BBZ, University Leipzig, Leipzig, Germany. Contact e-mail: [email protected] Alzheimer‘s disease (AD) is the most common form of dementia and affects nearly 10% of the population older than 65 years. Despite all progress in recent years a valid biomarker is still missing. Currently, combined clinical examinations and measurement of the biochemical markers ␤-amyloid and tau in cerebrospinal fluid (CSF) has become a valuable diagnostic tool to diagnose more than 80% of AD cases. Our work aims are to identify novel biomarkers in serum or cerebrospinal fluid by two-dimensional gel electrophoresis (2-DE). The presence of high-abundant proteins, such as serum albumin and immunoglobulins, in the human biological fluids often obscures lower-abundant proteins that could serve as important diagnostic markers of viable targets for therapeu-