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ABSTRACT: Blood-based tests for a rapid and valid diagnosis as well as outcome prognosis of acute stroke are desirable. Recently, plasma Aβ40 was suggested as an independent cerebrovascular risk factor candidate.
We investigated eight plasma samples of patients with clinical signs of acute cerebral ischemia for derangements of plasma amyloid-beta (Aβ) peptide patterns as compared to 13 patients with other neuropsychiatric diseases. For the analysis of plasma, we used immunoprecipitation followed by the quantitative Aβ-SDS-PAGE/immunoblot.
The major outcome was a striking decrease of Aβ1-40 in plasma paralleled by an increase in the ratio of Aβ1-38/Aβ1-40 in two patients with acute stroke. Interestingly, these patients had an onset of symptoms within only 2-4 hr before venous puncture and there was a strong correlation of Aβ1-38/Aβ1-40 levels with the time span between onset of symptoms and venous puncture.
From these results, we suggest the ratio of plasma Aβ1-38/Aβ1-40 as a possible biomarker for the early diagnosis of acute stroke.
Journal of Clinical Laboratory Analysis 07/2012; 26(4):238-45. · 1.38 Impact Factor
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ABSTRACT: Determination of amyloid β (Aβ) isoforms and in particular the proportion of the Aβ 1-42 isoform in cerebrospinal fluid (CSF) of patients suspected of Alzheimer's disease might help in early diagnosis and treatment of that illness. Due to the low concentration of Aβ peptides in biological fluids, a preconcentration step prior to the detection step is often necessary. This study utilized on-chip immunoprecipitation, known as micro-immunoprecipitation (μIP). The technique uses an immunosorbent (IS) consisting of magnetic beads coated with specific anti-Aβ antibodies organized into an affinity microcolumn by a magnetic field. Our goal was to thoroughly describe the critical steps in developing the IS, such as selecting the proper beads and anti-Aβ antibodies, as well as optimizing the immobilization technique and μIP protocol. The latter includes selecting optimal elution conditions. Furthermore, we demonstrate the efficiency of anti-Aβ IS for μIP and specific capture of 5 Aβ peptides under optimized conditions using various subsequent analytical methods, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), capillary electrophoresis, microchip electrophoresis, and immunoblotting. Synthetic Aβ peptides samples prepared in buffer and spiked in human CSF were analyzed. Finally, on-chip immunoprecipitation of Aβ peptides in human CSF sample was performed.
Biomicrofluidics 06/2012; 6(2):24126-2412612. · 3.37 Impact Factor
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ABSTRACT: Cerebrospinal fluid (CSF) concentrations of total Tau and Tau phosphorylated at threonine (position 181 [pTau181]) were studied
with ELISA in a group of carefully selected patients with a neurochemically supported diagnosis of Alzheimer’s disease (AD,
n=9; age range, 51–89 yr) and in a group of sex- and age-matched nondemented controls (n=9; age range, 52–81 yr). The concentration of both biomarkers is increased significantly in the AD group (total Tau, p<0.0008; pTau181, p<0.008). A significant correlation between CSF concentrations of both biomarkers is observed (R=0.897; p<0.001). Neither total Tau nor pTau181 correlates with age or degree of memory impairment, and only a tendency is observed
between the concentrations of total Tau and Aβ42 in the CSF. Our results further confirm a possible role of pTau181 as a diagnostic
tool in AD. The current literature regarding the physiological and pathological role of phosphorylated Tau proteins is reviewed,
as well as the role of these proteins as promising biomarkers in the diagnosis of neurodegenerative disorders.
Journal of Molecular Neuroscience 04/2012; 23(1):115-122. · 2.50 Impact Factor
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ABSTRACT: Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed as a powerful MS imaging (MSI) tool for the direct investigation of element distributions in biological tissues. Here, this technique was adapted for the analysis of native mouse spinal cord cryosections of 3.1 mm × 1.7 mm by implementing a new conventional ablation system (NWR-213) and improving the spatial resolution from 120 μm to 65 μm in routine mode. Element images of the spinal cord are provided for the first time and the metalloarchitecture was established using a multimodal atlas approach. Furthermore, the spatial distribution of Rb was mapped for the first time in biological tissue. Metal concentrations were quantified using matrix-matched laboratory standards and normalization of the respective ion intensities to the average (13)C ion intensity of standards and samples as a surrogate of slice thickness. The "butterfly" shape of the central spinal grey matter was visualized in positive contrast by the distributions of Fe, Mn, Cu and Zn and in negative contrast by C and P. Mg, Na, K, S and Rb showed a more homogenous distribution. The concentrations averaged throughout grey matter and white matter were 8 and 4 μg g(-1) of Fe, 3 and 2 μg g(-1) of Cu, 8 and 5 μg g(-1) of Zn, 0.4 and 0.2 μg g(-1) of Mn. The carbon concentration in white matter exceeded that of grey matter by a factor of 1.44. Zn and Cu at 9 and 4 μg g(-1), respectively, were particularly enriched in the laminae I and II, in line with the high synaptic and cellular density there. Surprisingly Zn but not Cu was enriched in the central channel. Rb occurred at 0.3 μg g(-1) with a distribution pattern congruent to that of K. The coefficients of variation were 6%, 5%, 8% and 10% for Fe, Cu, Zn and Mn, respectively, throughout three different animals measured on different days. These MSI analyses of healthy wild type spinal cords demonstrate the suitability of the established techniques for investigating diseased or transgenic states in future imaging studies.
Metallomics 02/2012; 4(3):284-8. · 3.90 Impact Factor
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Stefan Lehnert,
Sarah Jesse,
Wolfgang Rist,
Petra Steinacker,
Hilkka Soininen,
Sanna-Kaisa Herukka,
Hayrettin Tumani,
Martin Lenter,
Patrick Oeckl,
Boris Ferger,
Bastian Hengerer, Markus Otto
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ABSTRACT: About 30% of patients with Parkinson's disease (PD) develop Parkinson's disease dementia (PDD) in the course of the disease. Until now, diagnosis is based on clinical and neuropsychological examinations, since so far there is no laboratory marker. In this study we aimed to find a neurochemical marker which would allow a risk assessment for the development of a dementia in PD patients. For this purpose, we adopted a gel-free proteomic approach (iTRAQ-method) to identify biomarker-candidates in the cerebrospinal fluid (CSF) of patients with PD, PDD and non-demented controls (NDC). Validation of these candidates was then carried out by multiple-reaction-monitoring (MRM) optimised for CSF. Using the iTRAQ-approach, we were able to identify 16 differentially regulated proteins. Fourteen out of these 16 proteins could then be followed-up simultaneously in our optimised MRM-measurement protocol. However only Tyrosine-kinase-non-receptor-type 13 and Netrin-G1 differed significantly between PDD and NDC cohorts. In addition, a significant difference was found for Golgin-160 and Apolipoprotein B-100 between PD and NDC. Apart from possible pathophysiological considerations, we propose that Tyrosine-kinase non-receptor-type 13 and Netrin G1 are biomarker candidates for the development of a Parkinson's disease dementia. Furthermore we suggest that iTRAQ and MRM are valuable tools for the discovery of biomarker in cerebrospinal fluid. However further validation studies need to be done with larger patient cohorts and other proteins need to be checked as well.
Experimental Neurology 02/2012; 234(2):499-505. · 4.70 Impact Factor
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Sarah Jesse,
Stefan Lehnert,
Olaf Jahn,
Lucilla Parnetti,
Hilkka Soininen,
Sanna-Kaisa Herukka,
Petra Steinacker,
Saskia Tawfik,
Hayrettin Tumani,
Christine A F von Arnim,
Manuela Neumann,
Hans A Kretzschmar,
Hasan Kulaksiz,
Martin Lenter,
Jens Wiltfang,
Boris Ferger,
Bastian Hengerer, Markus Otto
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ABSTRACT: The prevalence of Parkinson's disease (PD) increases with age. Up to 50% of PD show cognitive decline in terms of a mild cognitive impairment already in early stages that predict the development of dementia, which can occur in up to 80% of PD patients over the long term, called Parkinson's disease dementia (PDD). So far, diagnosis of PD/PDD is made according to clinical and neuropsychological examinations while laboratory data is only used for exclusion of other diseases. The aim of this study was the identification of possible biomarkers in cerebrospinal fluid (CSF) of PD, PDD and controls (CON) which predict the development of dementia in PD. For this, a proteomic approach optimized for CSF was performed using 18 clinically well characterized patients in a first step with subsequent validation using 84 patients. Here, we detected differentially sialylated isoforms of Serpin A1 as marker for differentiation of PD versus PDD in CSF. Performing 2D-immunoblots, all PDD patients could be identified correctly (sensitivity 100%). Ten out of 24 PD patients showed Serpin A1 isoforms in a similar pattern like PDD, indicating a specificity of 58% for the test-procedure. In control samples, no additional isoform was detected. On the basis of these results, we conclude that differentially sialylated products of Serpin A1 are an interesting biomarker to indicate the development of a dementia during the course of PD.
PLoS ONE 01/2012; 7(11):e48783. · 4.09 Impact Factor
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ABSTRACT: Aggregation of beta amyloid peptides especially Aβ1-42 in amyloid plaques is one of the major -neuropathological events in Alzheimer's disease. This event is normally accompanied by a relative reduction of the concentration of Aβ1-42 in the cerebrospinal fluid (CSF) of patients developing the signs of Alzheimer's disease. Here, we describe a microchip gel electrophoresis method in a polydimethylsiloxane (PDMS) chip that enables rapid profiling of major Aβ peptides. The method was applied to compare the relative concentration of Aβ1-42 with other Aβ peptides, for example, Aβ 1-40 in CSF. In order to increase the sensitivity of detection, Aβ peptides in the CSF samples were first captured and concentrated using magnetic beads coated with specific anti-Aβ antibodies.
Methods in molecular biology (Clifton, N.J.) 01/2012; 869:173-84.
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Elena Lebedeva,
Julia C Stingl,
Dietmar R Thal,
Estifanos Ghebremedhin,
Joachim Strauss,
Esra Özer,
Lars Bertram,
Björn von Einem,
Hayrettin Tumani, Markus Otto,
Matthias W Riepe,
Josef Högel,
Albert C Ludolph,
Christine A F von Arnim
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ABSTRACT: Beta-amyloid 42 (Aβ42) concentrations in cerebrospinal fluid (CSF) are significantly decreased in Alzheimer's disease (AD). The aim of this study was to correlate genetic variability in presenilin 2 (PSEN2) in relation to Aβ42 concentrations and to confirm association of apolipoprotein E (APOE) alleles E4/E4 genotype with lower CSF Aβ42. Haplotype analysis of PSEN2 and APOE genotyping were performed in 175 Alzheimer's disease patients, as defined by clinical diagnosis and Aβ42 levels. One distinct haploblock in PSEN2 was detected and the frequent haplotypes were analyzed using 4 tagging single nucleotide polymorphisms (SNPs). We found an association between haplotype 2 and higher CSF Aβ42 concentrations (p = 0.021) and lower Aβ42 concentrations in haplotype 5 carriers (p < 0.001). APOE E4/E4 carriers had lower Aβ42 levels (p = 0.009). Additive regression analysis showed an association of Aβ42 level with APOE genotype (p = 0.024), haplotype 4 (p = 0.064), and haplotype 5 (p = 0.04), whereas gender, age at onset and Mini Mental State Examination (MMSE) remained insignificant. Using CSF Aβ42 as a biomarker we replicated genetic influences in APOE and observed a significant influence of a new haplotype in PSEN2. A better understanding of genetic influences on biomarkers like CSF Aβ42 might help to stratify patients and develop specific treatment strategies.
Neurobiology of aging 01/2012; 33(1):201.e9-18. · 5.94 Impact Factor
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ABSTRACT: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are important second messengers and are potential biomarkers for Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Creutzfeldt-Jakob disease (CJD).
Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS) the cerebrospinal fluid (CSF) concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15) had lower cAMP (-70%) and cGMP (-55%) concentrations in CSF compared with controls (n = 11). There was no difference in PD, PD dementia (PDD) and ALS cases. Receiver operating characteristic (ROC) curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC) of 0.86 (cAMP) and 0.85 (cGMP). We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92) and to 93% and 100% for the ratio tau/cAMP (AUC 0.99).
We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.
PLoS ONE 01/2012; 7(3):e32664. · 4.09 Impact Factor
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Markus Otto,
Robert Bowser,
Martin Turner,
James Berry,
Johannes Brettschneider,
James Connor,
Júlia Costa,
Merit Cudkowicz,
Jonathan Glass,
Olaf Jahn, [......],
Lucilla Parnetti,
Axel Petzold,
Pamela Shaw,
Alexander Sherman,
Petra Steinacker,
Sigurd Süssmuth,
Charlotte Teunissen,
Hayrettin Tumani,
Anna Wuolikainen,
Albert Ludolph
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ABSTRACT: Despite major advances in deciphering the neuropathological hallmarks of amyotrophic lateral sclerosis (ALS), validated neurochemical biomarkers for monitoring disease activity, earlier diagnosis, defining prognosis and unlocking key pathophysiological pathways are lacking. Although several candidate biomarkers exist, translation into clinical application is hindered by small sample numbers, especially longitudinal, for independent verification. This review considers the potential routes to the discovery of neurochemical markers in ALS, and provides a consensus statement on standard operating procedures that will facilitate multicenter collaboration, validation and ultimately clinical translation.
Amyotrophic Lateral Sclerosis 01/2012; 13(1):1-10. · 3.40 Impact Factor
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ABSTRACT: Among the first reported functions of 14-3-3 proteins was the regulation of tyrosine hydroxylase (TH) activity suggesting a possible involvement of 14-3-3 proteins in Parkinson's disease. Since then the relevance of 14-3-3 proteins in the pathogenesis of chronic as well as acute neurodegenerative diseases, including Alzheimer's disease, polyglutamine diseases, amyotrophic lateral sclerosis and stroke has been recognized. The reported function of 14-3-3 proteins in this context are as diverse as the mechanism involved in neurodegeneration, reaching from basal cellular processes like apoptosis, over involvement in features common to many neurodegenerative diseases, like protein stabilization and aggregation, to very specific processes responsible for the selective vulnerability of cellular populations in single neurodegenerative diseases. Here, we review what is currently known of the function of 14-3-3 proteins in nervous tissue focussing on the properties of 14-3-3 proteins important in neurodegenerative disease pathogenesis.
Seminars in Cell and Developmental Biology 09/2011; 22(7):696-704. · 6.65 Impact Factor
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ABSTRACT: Patients with meningitis are often difficult to classify into bacterial (BM) or benign viral (VM) meningitis. To facilitate the differential diagnosis, S100B and Tau protein in the cerebrospinal fluid (CSF) were measured and compared with standard laboratory parameters.
S100B(CSF), Tau(CSF), and routine parameters (CSF leukocyte count, protein(CSF), lactate(CSF), serum C-reactive protein, blood leukocyte count and body temperature) were analyzed in 33 patients with microbiologically confirmed BM and in 19 with VM. Their classification accuracy, sensitivity and specificity were studied by receiver operating characteristic (ROC) curves.
S100B(CSF) concentrations were higher in BM than in VM patients (p = 0.03) and showed a promising accuracy (90%) for the differential diagnosis of BM versus VM. Its discriminative properties were comparable to routine parameters. Of all parameters, S100B(CSF) showed the highest specificity (100%) with an optimal cut-off of 3.1 ng/ml. Tau(CSF) concentrations were useless for the discrimination (p = 0.64).
In contrast to Tau(CSF), S100B(CSF) concentrations ≥3.1 ng/ml are promising to discriminate bacterial from viral meningitis.
European Neurology 08/2011; 66(3):128-32. · 1.81 Impact Factor
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Niklas Mattsson,
Ulf Andreasson,
Staffan Persson,
Hiroyuki Arai,
Sat Dev Batish,
Sergio Bernardini,
Luisella Bocchio-Chiavetto,
Marinus A Blankenstein,
Maria C Carrillo,
Sonia Chalbot, [......],
Hayrettin Tumani,
Robert M Umek,
Bianca Van Broeck,
Hugo Vanderstichele,
Laszlo Vecsei,
Marcel M Verbeek,
Manfred Windisch,
Jing Zhang,
Henrik Zetterberg,
Kaj Blennow
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ABSTRACT: The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Mölndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples.
Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories.
Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.
Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2011; 7(4):386-395.e6. · 5.90 Impact Factor
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Acta Neurovegetativa 06/2011; · 2.73 Impact Factor
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Hayrettin Tumani,
Florian Deisenhammer,
Gavin Giovannoni,
Ralf Gold,
Hans-Peter Hartung,
Bernhard Hemmer,
Reinhard Hohlfeld, Markus Otto,
Martin Stangel,
Brigitte Wildemann,
Uwe K Zettl
Annals of Neurology 06/2011; 70(3):520; author reply 521. · 11.09 Impact Factor
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ABSTRACT: Appropriate treatment of dementia requires biomarkers that provide an exact and differential diagnosis. We recently presented differentially expressed amyloid-β (Aβ) peptide patterns in cerebrospinal fluid (CSF) as biomarker candidates for neurochemical diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The objective of the present study was to investigate CSF Aβ peptide patterns in both neuropathologically and clinically defined diagnostic groups of AD and DLB. Using the quantitative Aβ-SDS-PAGE/immunoblot, we analyzed CSF samples of neuropathologically defined patients with AD (definite AD, dAD; n = 11) and DLB (definite, dDLB; n = 12). We compared absolute and relative quantities of CSF Aβ-peptides with a larger cohort of clinically diagnosed patients with probable AD (pAD; n = 71), probable DLB (pDLB; n = 32), and non-demented controls (NDC; n = 71). Each neuropathologically and clinically defined diagnostic group showed a similar relative distribution of CSF Aβ-peptides (Aβ(1-X%)). Aβ(1-42%) was lowered in dAD compared to NDC (p = 1.6 × 10⁻⁷, but did not differ between dAD and pAD. Aβ(1-40ox%) was elevated in dDLB as compared to NDC (p = 1.8 × 10⁻⁵, but did not differ between dDLB and pDLB. Thus, we were able to confirm previous results on Aβ peptide patterns in neuropathologically characterized patients with AD and DLB. Our results underline the usefulness of the CSF Aβ(1-42%) and Aβ(1-40ox%) as diagnostic biomarkers for AD and DLB, respectively.
Journal of Alzheimer's disease: JAD 02/2011; 24(2):383-91. · 3.74 Impact Factor
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ABSTRACT: We report a CE-LIF method for the separation and detection of five synthetic amyloid-β peptides corresponding to an important family of CSF-biomarkers in the context of Alzheimer disease (AD). The presumed most relevant peptides (Aβ1-42, Aβ1-40, and Aβ1-38) that may support the differentiation between AD and healthy patients or other dementias were successfully detected in CSF by incorporating an immunoconcentration step prior to CE analysis of derivatized peptides. We labeled the Aβ peptides with a fluoroprobe dye before CE-LIF analysis. This reagent reacts with the amino groups of lysine residues and produced mostly ditagged Aβ peptides under the proposed experimental conditions. The labeling reaction displayed similar efficiency with each one of the five different synthetic Aβ peptides that were tested. The limit of detection of the CE-LIF method approached 280 attomoles of injected synthetic labeled Aβ peptides. We obtained excellent correlation between peak areas and peptide concentrations from 35 nM to 750 nM. For the detection of Aβ peptides in human CSF samples, we enriched the peptides by immunoprecipitation prior to the CE-LIF analysis. The comparison of the CE-LIF profiles obtained from CSF samples from 3 AD patients and 4 non-demented control subjects indicated noticeable differences, suggesting that this method, which relies on a multibiomarker approach, may have potential as a clinical diagnostic test for AD.
Analytical Chemistry 02/2011; · 5.86 Impact Factor
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Brit-Maren M Schjeide,
Cathrin Schnack,
Jean-Charles Lambert,
Christina M Lill,
Julia Kirchheiner,
Hayrettin Tumani, Markus Otto,
Rudolph E Tanzi,
Hans Lehrach,
Philippe Amouyel,
Christine A F von Arnim,
Lars Bertram
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ABSTRACT: Two recent and simultaneously published genome-wide association studies independently implicated clusterin (CLU), complement receptor 1 (CR1), and phosphatidylinositol binding clathrin assembly protein (PICALM) as putative novel Alzheimer disease (AD) risk loci. Despite their strong statistical support, all 3 signals emerged from heterogeneous case-control populations and lack replication in different settings.
To determine whether genetic variants in CLU, CR1, and PICALM confer risk for AD in independent data sets (n = 4254) and to test the impact of these markers on cerebrospinal fluid (CSF)-Aβ42 and total-tau protein levels (n = 425).
Genetic association study using family-based and case-control designs.
Ambulatory or hospitalized care.
Family samples originate from mostly multiplex pedigrees recruited at different centers in the United States (1245 families, 2654 individuals with AD, and 1175 unaffected relatives). Unrelated case-control subjects originate from 1 clinical center in Germany (214 individuals with AD and 211 controls). All subjects were of European descent.
The association between 5 genetic variants in CLU, CR1, and PICALM and risk for AD, and the correlation between these 5 genetic variants and CSF-Aβ42 and tau levels.
All 3 investigated loci showed significant associations between risk for AD (1-tailed P values ranging from <.001 to .02) and consistent effect sizes and direction. For each locus, the overall evidence of association was substantially strengthened on meta-analysis of all available data (2-tailed P values ranging from 1.1 × 10(-16) to 4.1 × 10⁻⁷). Of all markers tested, only rs541458 in PICALM was shown to have an effect on CSF protein levels, suggesting that the AD risk allele is associated with decreased CSF Aβ42 levels (2-tailed P = .002).
This study provides compelling independent evidence that genetic variants in CLU, CR1, and PICALM are genetically associated with risk for AD. Furthermore, the CSF biomarker analyses provide a first insight into the potentially predominant pathogenetic mechanism(s) underlying the association between AD risk and PICALM.
Archives of general psychiatry 02/2011; 68(2):207-13. · 12.26 Impact Factor
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ABSTRACT: We determined cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ)(1-38), Aβ(1-40), Aβ(1-42), total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer's dementia (AD, n = 25) and nondemented controls (n = 20).
Commercially available ELISA and electrochemiluminescence methods were applied.
High CSF p-tau and low ratios of Aβ(1-42)/Aβ(1-40) and Aβ(1-42)/Aβ(1-38), respectively, were specific for AD. CSF Aβ(1-38) was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD.
This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations.
Dementia and Geriatric Cognitive Disorders 01/2011; 31(1):37-44. · 2.14 Impact Factor
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ABSTRACT: Decreased levels of β-amyloid (Aβ) 1-42 in cerebrospinal fluid (CSF) are characteristic for Alzheimer's disease (AD) and are also evident in Creutzfeldt-Jakob disease (CJD). Aβ plaques are thought to be responsible for this decrease in AD patients, whereas such Aβ plaques are rarely seen in CJD. To investigate the Aβ pattern in brain and CSF of neuropathologically confirmed CJD and AD patients we used an electrophoretic method to investigate Aβ peptide fractions which are not accessible to ELISA and immunohistochemistry. We analyzed Aβ peptides in the CSF of autopsy-confirmed CJD and AD patients and the corresponding brain homogenates using a quantitative urea-based Aβ electrophoresis immunoblot (Aβ-SDS-PAGE/immunoblot).The CSF Aβ1-42 decrease correlated with the brain Aβ load in AD, but not in CJD. There was no difference in the soluble fractions of brain homogenate in AD and CJD. We therefore conclude that different mechanisms in AD and CJD are responsible for the Aβ1-42 decrease in the CSF.
Acta Neurovegetativa 01/2011; 118(5):691-7. · 2.73 Impact Factor
