Evaluation of the diagnostic performance of Alpha-1-Antitrypsin in early detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) constitutes one of the most frequent cancer types and accounting the vast majority of tumour-related fatalities worldwide. HCC is remain related to a bad prognosis in patients with an advanced disease stage. This study was conducted to evaluate the relationship between A1AT concentration, A1AT gene promoter methylation, and A1AT genotype variation, and HCC risk. In this case-control research, we investigated A1AT levels in plasma as a diagnostic biomarker for the earlier detection of HCC in 100 patient samples. We also checked DNA promoter methylation of the A1AT gene, and genotypes in all the studied groups. The levels of AFP and A1AT in plasma were determined using ELISA and nephelometric techniques, respectively. The genomic DNA extracted from blood samples has been examined for S and Z genotypes using the PCR-RFLP technique, as well as gene A1AT promoter methylation was assessed by methylation specific-PCR assay.The plasma data analysis showed that there was a significant difference between HCC and healthy control samples regarding the level of AFP and A1AT. The range of plasma A1AT concentration was 166.6±27.28g/L in patients and 129.8±15.87g/L in controls (p <0.001).  A1AT concentration was also associated with progressive tumour stages. Moreover, the roc curve stated that A1AT concentration is better in sensitivity than using AFP in early detection of HCC cancer patients as A1AT concentration at 135mg/L, had a sensitivity of 99% and a specificity of 79% for distinguishing cancer patients from healthy individuals. We concluded that the plasma A1AT concentration has higher sensitivity than AFP for early detection of HCC.

Chemical characteristics and cancer risk assessment of smokeless tobacco used in Tunisia (neffa).

INTRODUCTION: neffa, a form of air-dried smokeless tobacco used in North Africa, is spuriously perceived as a lower risk alternative to smoking. The objective of this study was to provide information on some harmful constituents of neffa and to use them for cancer risk assessment. METHODS: a high-performance liquid chromatography method coupled with fluorescence detector was used to determine polycyclic aromatic hydrocarbons (PAHs) in one sample of neffa. An atomic absorption spectrometry was performed to determine the concentrations of lead and cadmium in three samples of neffa. The levels of toxicants found in neffa were used to assess for lifetime cancer risk as advocated by the US Environment Protection Agency. RESULTS: the determination of PAHs in neffa allowed the identification of phenanthrene and anthracene. However, the higher molecular weight PAHs such as Benzo(a)Pyrene B(a)P were not detected. The concentrations of cadmium and lead varied between 1.3 to 2.8µg/g and 1.7 to 4.6µg/g respectively. Cancer risk for cadmium and lead varied between 4.2E-03 to 9.3E-03 and 2.5E-06 to 6.4E-06 respectively. Cancer risk for Cd exceeded the range of 10E-04 to 10E-06 of an acceptable risk. CONCLUSION: neffa is not a healthy alternative for overcoming smoking addiction. It contains mineral and organic pulmonary toxicants. This study could serve as a scientific basis to inform consumers about the products´ toxicity and help them to quit smokeless tobacco (SLT) use.

Maillard Reaction Products and Phenolic Compounds from Roasted Peanut Flour Extracts Prevent Scopolamine-Induced Amnesia Via Cholinergic Modulation and Antioxidative Effects in Mice.

Research on the beneficial effects of Maillard reaction products (MRPs) and phenolic compounds derived from roasted peanut flour on the nervous system remains insufficient. This study aimed to evaluate the effect of a 28-day oral administration of defatted peanut extract rich in MPRs and polyphenolic compounds on the cognitive impairments and oxidative injury induced by scopolamine in a mouse model. Light and dark extracts from peanut flour were prepared by heating peanuts at 187°C for two different times (8.6 and 12.7 min) and defatted using soxhlet apparatus. The mice were orally pretreated with either roasted defatted peanuts extracts (100 mg/kg) or donepezil (3 mg/kg) for 21 days. On day 19 and until day 28, mice were injected subcutaneously with water or scopolamine (1 mg/kg body weight) 15 min after roasted defatted peanuts extracts/water feeding. Mice were subsequently subjected to a battery of behavioral tests including open field locomotor activity assay, and Morris water maze test. Brain tissues were collected to measure acetylcholine, acetylcholinesterase, and oxidative parameters (glutathione and malondialdehyde). Roasted defatted peanuts (light and dark) (100 mg/kg) treatment significantly ameliorated cognitive performance and reversed the oxidative damage when compared with the scopolamine group. These data demonstrate the defatted peanuts extracts exert potent anti-amnesic effects via the modulation of cholinergic and antioxidant activities.

Arthrophytum scoparium Extract Improves Memory Impairment and Affects Acetylcholinesterase Activity In Mice Brain.

BACKGROUND: Arthrophytum scoparium (Pomel) Iljin (Amaranthaceae family) has been widely used in traditional Tunisian medicine to treat many disorders such as migraine, headache, and neurological disorders. This study investigates the effect of Arthrophytum scoparium Aqueous Extract (ASAE) on cognitive impairments and oxidative injury induced by galactose (10%) in a mouse model. MATERIALS AND METHODS: The mice were divided randomly into 4 experimental groups, including the control group (saline water 9 ‰), Galactose group, Scop group (300 mg/kg/d), and Scop+Gal group (300 mg/kg/d). Mice received the corresponding solutions by intraperitoneal injection (i.p.) for 7 days before the Y-maze active tests. Galactose 10% was given to all groups except control and Scop groups, 30 min before the trial. Levels of Acetylcholinesterase Activity (AChE), Ascorbic Acid (AA), Gluthatione (GSH) and Malondialdehyde (MDA) in mice brains were examined. RESULTS: Chronic administration of galactose significantly impaired cognitive performance in Y maze, caused marked oxidative damages and a significant increase in the acetylcholinesterase activity as compared to other groups. On the contrary, ASAE (300 mg/kg) treatment suppressed galactoseinduced oxidative damage by ameliorating the increased levels of GSH and AA. Moreover, ASAE treatment reduced brain AChE activities in the galactose-induced model. CONCLUSION: These findings suggest that ASAE exerts potent anti-amnesic effects via the modulation of cholinergic and antioxidant activities. The observed pharmacological activities should be further evaluated by detailed experimental studies and validated by clinical trials.

Effects of Carpobrotus edulis Extract on Oxidative Stress and 158N Oligodendrocyte Death.

OBJECTIVE: Age-related diseases, including neurodegenerative diseases, are associated with oxidative stress and lipid peroxidation, and increase the levels of cholesterol auto-oxidation products such as 7ß-hydroxycholesterol (7ß-OHC). Thus, it is imperative to identify agents that can prevent 7ß-OHC-induced side-effects. METHODS: We evaluated the potential protective effects of Carpobrotus edulis ethanol-water extract (EWe) on murine oligodendrocytes (158N) cultured in the absence or presence of 7ß-OHC (20 µg/mL, 24 h). The cells were incubated with EWe (20-200 µg/mL) 2 h before 7ß-OHC treatment. Mitochondrial activity and cell growth were evaluated with the MTT assay. Photometric methods were used to analyze antioxidant enzyme [catalase (CAT) and glutathione peroxidase (GPx)] activities and the generation of lipid and protein oxidation products [malondialdehyde (MDA), conjugated diene (CD), and carbonylated proteins (CPs)]. RESULTS: Treatment with 7ß-OHC induced cell death and oxidative stress (reflected by alteration in CAT and SOD activities). Overproduction of lipid peroxidation products (MDA and CDs) and CPs was also reported. The cytotoxic effects associated with 7ß-OHC were attenuated by 160 µg/mL of EWe of C. edulis. Cell death induced by 7ß-OHC treatment was ameliorated, GPx and CAT activities were restored to normal, and MDA, CD, and CP levels were reduced following C. edulis extract treatment. CONCLUSION: These data demonstrate the protective activities of C. edulis EWe against 7ß-OHC-induced disequilibrium in the redox status of 158N cells, indicative of the potential role of this plant extract in the prevention of neurodegenerative diseases.

7ß-hydroxycholesterol-induced cell death, oxidative stress, and fatty acid metabolism dysfunctions attenuated with sea urchin egg oil.

Some oxysterols resulting either from enzymatic oxidation or autoxidation of cholesterol are associated with age-related diseases including neurodegenerative diseases. Among these oxysterols, 7ß-hydroxycholesterol (7ß-OHC) is often found at increased levels in patients. It is therefore important to identify molecules or mixtures of molecules to prevent 7ß-OHC-induced side effects. Consequently, murine oligodendrocytes (158N) were cultured in the absence or presence of 7ß-OHC (20 µg/mL, 24 h) with or without a natural oil extracted from sea urchin (Paracentrotus lividus) eggs known for its biological activity. Firstly, the chemical composition of this oil was determined using 31P NMR and GC-MS. Secondly, this oil was used to reduce 7ß-OHC-induced side effects. To this end, the oil (160 µg/mL) was added to the culture medium of 158N cells 2 h before 7ß-OHC. The effects of 7ß-OHC with or without the oil on cell viability were studied with the MTT test. Photometric methods were used to analyze antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as the generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation product (carbonylated proteins (CPs)). Gas chromatography was used to determine the fatty acid profile. With 7ß-OHC, an induction of cell death associated with oxidative stress (alteration of GPx and SOD activities) was observed; an overproduction of lipid peroxidation products (MDA and CDs) and CPs was also revealed. Sea urchin egg oil attenuated 7ß-OHC-induced cytotoxicity: 7ß-OHC-induced cell death was reduced, GPx and SOD activities were normalized, and lower levels of MDA, CDs and CPs were produced. In addition, whereas a disturbed fatty acid profile was observed with 7ß-OHC, similar fatty acid profiles were found in control cells and in cells cultured with 7ß-OHC associated with sea urchin egg oil. These data demonstrate the protective activities of sea urchin egg oil against 7ß-OHC-induced side effects on 158N cells, supporting the concept that this oil may have benefits in the prevention of neurodegenerative diseases.

Characterization, antioxidant and antiglycation properties of polysaccharides extracted from the medicinal halophyte Carpobrotus edulis L.

In this study, Box-Behnken design was used to optimize the ultrasonic extraction of Carpobrotus edulis polysaccharides (CEP), and the effect of time, extraction temperature and water to material ratio was evaluated. Optimum conditions were 1.77h, 78.0°C and 33.04mL/g to improved CEP yield (7.84%), which is in good agreement with the predicted yield 7.77%. Then, the physico-chemical, antioxidant and antiglycation properties of optimized CEP were studied, and the total sugar and galacturonic acid content were 89.7 and 63.2%, respectively. The composition of neutral monosaccharide was arabinose, xylose, rhamnose and mannose in the molar percentage of 71.84, 14.80, 8.57, and 4.79%, respectively. In addition, (1H, and 13C) NMR and FTIR analyses confirmed the presence of uronic acids in the free and methyl ester forms with a degree of esterification of 31.27%. Therefore, this finding showed that CEP is a low methoxyl pectic polysaccharide, with an average molecular weight about 65,000g/mol. Finally, the results indicated that CEP presents strong antioxidant activities in vitro (DPPH, chelating ability and reducing power), and significantly inhibits lipid peroxidation and the formation of fluorescent advanced glycation end products in glucose-BSA system model.

Effect of ultrasonic degradation of hyaluronic acid extracted from rooster comb on antioxidant and antiglycation activities.

CONTENT: Recently, low-molecular-weight hyaluronic acid (LMWHA) has been reported to have novel features, such as free radical scavenging activities, antioxidant activities and dietary supplements. OBJECTIVE: In this study, hyaluronic acid (HA) was extracted from rooster comb and LMWHA was obtained by ultrasonic degradation in order to assess their antioxidant and antiglycation activities. MATERIALS AND METHODS: Molecular weight (Mw) and the content of glucuronic acid (GlcA) were used as the index for comparison of the effect of ultrasonic treatment. The effects on the structure were determined by ultraviolet (UV) spectra and Fourier transform infrared spectra (FTIR). The antioxidant activity was determined by three analytical assays (DPPH, NO and TBARS), and the inhibitory effect against glycated-BSA was also assessed. RESULTS: The GlcA content of HA and LMWHA was estimated at about 48.6% and 47.3%, respectively. The results demonstrate that ultrasonic irradiation decreases the Mw (1090-181 kDa) and intrinsic viscosity (1550-473 mL/g), which indicate the cleavage of the glycosidic bonds. The FTIR and UV spectra did not significantly change before and after degradation. The IC50 value of HA and LWMHA was 1.43, 0.76 and 0.36 mg/mL and 1.20, 0.89 and 0.17 mg/mL toward DPPH, NO and TBARS, respectively. Likewise LMWHA exhibited significant inhibitory effects on the AGEs formation than HA. DISCUSSION AND CONCLUSION: The results demonstrated that the ultrasonic irradiation did not damage and change the chemical structure of HA after degradation; furthermore, decreasing Mw and viscosity of LMWHA after degradation may enhance the antioxidant and antiglycation activity.

Inhibition of protein glycation, antioxidant and antiproliferative activities of Carpobrotus edulis extracts.

Carpobrotus edulis is an important South African medicinal plants used as a food and therapeutic agent in traditional medicine. The aim of this study was to determine the phytochemical content, antioxidant, antiglycation and cytotoxic effect against Human Colon Cancer Cell Line (HCT-116) of aqueous and ethanol-water (1:1v/v) extracts of Carpobrotus edulis.The content of total phenolics and flavonoids in aqueous and ethanol-water extract were 151.99µg and 66.35µg gallic acid equivalents/mg of dry extract, and 38.84µg and 21.96µg quercetin/mg of dry extract, respectively. Furthermore, phenolic compositions analysis indicated the presence of seven majority compounds including sinapic acid, ferulic acid, luteolin7-o-glucoside, hyperoside, isoquercitrin, ellagic acid and isorhamnetin 3-O-rutinoside. The ethanol-water extract (100-1000µg/mL) showed better antioxidant activity than aqueous extract. Furthermore, Carpobrotus edulis extracts, especially ethanol-water extract significantly inhibited the formation of fluorescent advanced glycation end products, prevented oxidation-induced protein damage and exhibited a cytotoxic effect against HCT116 cells, with a significant decrease in cell viability after 24h of incubation. The results obtained suggest that the Carpobrotus edulis extracts could be used as an easily accessible source of natural antioxidants and as potential phytochemicals against protein glycation and colon cancer.

[Biological assay for galactose-1 phosphate measurement application in subjects with galactosemia]. / Dosage du galactose-1 phosphate et application chez des sujets galactosémiques.

Congenital galactosemia is a hereditary, autosomal recessive and metabolic disease. It is linked to an enzyme deficiency, more commonly known by the deficiency of galactose-1- phosphate uridyltransferase (GALT), which is responsible for an accumulation of galactose-1- phosphate in the blood. Clinical symptoms appear early in infancy from the second week of life. They generally manifested by some disorders within liver, kidney, eye, gastrointestinal, neurological and also with cataracts. Currently, the clinical diagnosis remains difficult hence the importance of further investigations based on effective biological assessments to highlight the disease. The diagnosis of galactosemia is made by the laboratory test. The latter includes the determination of Gal-1-P which is done by a fluorometric method spot test. This study was conducted in order to assess the repeatability, reproducibility, accuracy, and effectiveness of the techniques used. We have found the CV for a repeatability (CV = 5 %), reproducibility (CV = 4 %) which confirms the accuracy of the method proceeded in this study. This method allows us to have a degree of inaccuracy less than 1%. According to the study of the effectiveness of "spot test", we found that our technique is specific (Sp = 93 %) and sensitive (Se = 83 %).

[Maroteaux-Lamy syndrome: a case report]. / Syndrome de Maroteaux-Lamy : à propos d'un cas.

The Maroteaux-Lamy disease, or mucopolysaccharidosis type VI is an inherited metabolic disorder severe and rare. It is caused by a deficiency of the enzyme arylsulfatase B. It is characterized by a heterogeneous clinical, radiological and genetic. We report the case of a Maroteaux-Lamy syndrome of in a child aged 7 years whose diagnosis was suspected clinically by the combination of a dysmorphic syndrome, a failure to thrive not harmonious, hepatomegaly and normal intelligence. Radiological exams have objectified dysostosis multiplex. Biochemical analysis of urine showed the abnormal presence of dermatan sulfate. The determination of leukocyte enzyme activity confirmed the diagnosis by showing arylsulfatase B deficiency. Hence the diagnosis of syndrome Maroteaux-Lamy in its mild form (type B) was selected.

Folate and homocysteine in the cerebrospinal fluid of patients with Alzheimer's disease or dementia: a case control study.

BACKGROUND: Amyloid deposition in the brain is an early event in Alzheimer's disease (AD), but a dysfunction of the blood-brain barrier or a disturbance in the metabolism of folate and homocysteine (Hcy) may affect the development of dementia. We investigated if the concentrations of folate and Hcy would be modified in cerebrospinal fluid (CSF) of clinically diagnosed AD patients. METHODS: We included 70 AD patients, 33 patients with another type of dementia (nAD) and 30 age-matched control subjects. Plasma Hcy was assayed as well as Hcy, folate, Aß1-42 and T-tau in CSF. We used ANOVAs for comparison between groups, and then pairwise comparisons by Wilcoxon tests with Bonferroni-corrected p values. Correlations were tested with the Spearman's rank test. RESULTS: Levels of Aß1-42, T-tau and folates in CSF were significantly different between groups, but not Hcy. In addition, the average folate in CSF was lower in AD patients compared with controls (18.7 ± 2.4 vs. 20.3 ± 1.7 nmol/l, Bonferroni-corrected p value < 0.02). There was no correlation between Aß1-42 or T-tau and folate or Hcy in CSF, regardless of the group. In the AD group, there was a significant inverse correlation between Hcy and folate in CSF (ρ = -0.63, p < 0.0001), whereas in the nAD group, a significant correlation was found for Hcy between plasma and CSF (ρ = 0.59, p < 0.0005). CONCLUSION: The concentration of folate in CSF was found to be decreased in AD patients. These findings support the hypothesis of a possible role of folate in the onset or worsening of AD.

[Primary distal renal tubular acidosis: a case report]. / L'acidose tubulaire rénale distale primitive : à propos d'un cas.

The primary distal renal tubular acidosis is characterized biochemically by the inability of the kidney to produce appropriately acid urine in the presence of systemic metabolic acidosis or after acid loading (e.g. ammonium chloride). It is secondary to defective excretion of H(+) by the cells of the collecting duct. We report the observation of the child MC, 4-year-old, for whom the association of polyuria-polydipsia syndrome, a failure to thrive, nephrolithiasis, hypercalciuria, and especially a high urine pH in the presence of metabolic acidosis did evoke diagnosis of distal renal tubular acidosis. An urine acidification test with ammonium chloride was performed, the urinary pH was always higher than 5.5, thus confirming the diagnosis.

Polymorphism in apoA1 Influences High-Density Lipoprotein Cholesterol Levels but Is Not a Major Risk Factor of Alzheimer's Disease.

BACKGROUND: Apolipoprotein A1 (apoA1) is the major apolipoprotein constituent of the high-density lipoprotein (HDL) and is involved in reverse cholesterol transport. Variation in the apoA1 gene might influence the function of the protein and, thus, brain cholesterol metabolism, leading to an increased risk for Alzheimer's disease (AD). AIM: In the current report, we investigated the role of the functional apoA1 polymorphism (-75 G/A) as a genetic risk factor for AD in a Tunisian population. METHODS: 173 AD patients and 150 healthy controls were studied. RESULTS: No association was found between this genetic variation in apoA1 gene and the risk of AD. The presence of the (-75 G/A) A allele appeared, however, to be associated with lower levels of cerebrospinal fluid Aß42 and HDL cholesterol levels in sera. CONCLUSION: Our data support the observation that apoA1 polymorphism influences cholesterol metabolism and Aß42 deposition in the brain.

[The congenital afibrinogenemia: case report]. / L'afibrinogénémie congénitale: à propos d'un cas.

The deficiency in factor I or fibrinogen is a largely unknown genetic disease. It is a rare condition inherited as an autosomal recessive, whose clinical events are variable, ranging from moderate to minimal bleeding or cataclysmic hemorrhage. We report a case of congenital afibrinogenemia in a 17 years-old patient hospitalized in surgical ICU for hemoperitoneum medium abundance discovered by abdominal ultrasound performed before a picture of abdominopelvic pain lasting for 24 hours. Exploration led to the diagnosis of congenital afibrinogenemia with favorable evolution with a contribution of factor deficient. Through this case we raise the problem of congenital afibrinogenemia in diagnosis and the peculiarities of its management.

Analysis of association between bleomycin hydrolase and apolipoprotein E polymorphism in Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia. Several studies indicate a possible relationship between different genes and Alzheimer's disease. To further investigate, we have analyzed the association between the bleomycin hydrolase (BLMH) and apolipoprotein E (ApoE) polymorphisms in 93 AD patients and age- and sex-matched 113 controls from the Tunisian population. The frequency of ApoE epsilon 4 allele was found to differ significantly in AD patients compared to the control [29.5% vs. 8.8 (χ (2) = 26, df = 1, p < 0.001)] leading to an increased risk of AD in subjects with this allele (OR = 3.29, 95% CI = 1.7-6.5; p = 0.001]. This risk was found to decrease from OR = 8.4, CI = 3.3-23; p < 0.001 in subjects less than 75 years old to OR = 1.2, CI = 1.031-14; p = 0.0297 in subjects 75 years and older. No association was observed between carrying the BLMH-G genotype and AD in ε4 negative or positive subjects.

-1154G/A and -2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to beta-amyloid (1-42) and total tau protein.

Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (-2578C/A) and (-1154G/A) polymorphisms did not differ significantly between AD and control groups (p>0.05). In the subgroup of ApoE varepsilon4 carriers, the -2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE varepsilon4 status using logistic regression, the -2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the -2578A allele may be associated with the development of AD in the individuals with ApoE varepsilon4 allele. In addition, AD patients carrying the -2578A allele had lower Abeta42 (p=0.029) levels than those without this allele, particularly in subjects with ApoE varepsilon4 allele.

Evaluation of cerebrospinal fluid tau/beta-amyloid(42) ratio as diagnostic markers for Alzheimer disease.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. Cerebrospinal fluid (CSF) concentrations of amyloid beta (Abeta1-42) peptides and total tau proteins (T-tau) may serve as biomarkers for AD. AIM: The objective of this study was to investigate the usefulness of CSF Abeta1-42 and T-tau analyses in the diagnosis of AD with Tunisians. METHODS: We focused on three groups originating from Central Tunisian that matched in age (range 48-85): healthy controls (n = 53), AD patients (n = 93) and non-Alzheimer (nAD) dementia (n = 35) patients. Abeta1-42 and T-tau levels were measured in CSF by sandwich enzyme-linked immunosorbent assay. RESULTS: The ratio of T-tau/Abeta1-42 at baseline yielded a sensitivity of 85.3% for detection of AD and the specificity was 84.8% to differentiate controls and nAD dementia. CONCLUSION: Our findings confirm the use of T-tau/Abeta1-42 ratio in the discrimination of AD patients from all other patients.

CSF beta-amyloid 1-42 and tau in Tunisian patients with Alzheimer's disease: the effect of APOE epsilon4 allele.

Alzheimer's disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. An accurate, convenient and objective test to detect AD is urgently needed for efficient drug development and effective clinical use of emerging therapies. The aim of the present work is to investigate the usefulness of cerebrospinal fluid (CSF) beta-amyloid protein (Abeta1-42) and total tau protein (t-tau) analyses in the diagnosis of AD and whether apolipoprotein E (ApoE) epsilon4 allele is a factor for AD affecting Tunisian people. Abeta1-42 and t-tau levels were measured in CSF from AD patients (n=73), non-Alzheimer dementia (nAD, n=35) and healthy controls (HC, n=38) by sandwich enzyme-linked immunosorbent assay. Abeta1-42 levels were decreased and t-tau increased in AD patients. The combination of Abeta1-42 and t-tau at baseline yielded a sensitivity of 87.4% for detection of AD. The specificities were 97.3% for controls and 82.7% for other dementia. The ApoE epsilon4 allele frequency (29.5%) was significantly higher in the AD patients than in the nAD patients (17.1%) or in the control groups (9.5%). AD patients carrying ApoE epsilon4 allele had lower Abeta1-42 (p<0.001) levels than those without a epsilon4 allele. The combination of t-tau and Abeta1-42 is a robust and reliable assay that may be useful in discriminating cases at risk for AD such as ApoE epsilon4 allele carriers from nAD patients or from age-matched control subjects.