P-tau 181P Research Articles

POTENTIAL USE OF ROUTINE CSF PARAMETERS FOR THE DIFFERENTIAL DIAGNOSIS OF DEMENTIA DISEASES

netics, Ghent, Belgium). ROC curve analyses were performed to assess diagnostic power. Added diagnostic value was explored by comparing the Ab isoforms performance to the performance of the core AD CSF biomarkers: Ab 1-42, T-tau and P-tau 181P. Results: The Ab isoforms levels correlated moderately with MMSE scores and disease duration in the dementia due to AD group, suggesting a correlation with disease progression. CSF Ab 1-42 levels were lower in e4 carriers as compared to non-carriers. The diagnostic value of the Ab 1-42/Ab 1-40 ratio was better than the diagnostic performance of Ab 1-42 in most differential situations. The best biomarkers to discriminate dementia due to AD from FTDwereAb 1-42/Ab 1-37 and the relative value of Ab 1-42 (AUC1⁄4 0.851 and 0.831 respectively). The best biomarkers to distinguish dementia due to AD and DLBwere Ab 1-42/Ab 1-38 and Ab 1-42/T-tau (AUC 1⁄4 0.843 and 0.838 respectively). Conclusions: In conclusion, Ab isoforms increase the diagnostic performance of Ab 1-42 and they are of help for differential dementia diagnosis, especially to differentiate FTD and DLB from AD and to diagnose AD in patients with normal Ab 1-42 levels. Furthermore, in contrast to Ab 1-42, Ab isoforms are correlated with disease severity in AD.

A EUROPEAN BIOBANK FOR THE VALIDATION OF NEW MARKERS FOR ALZHEIMER'S AND PARKINSON’S DISEASE: THE BIOMARKAPD PROJECT

Background: The cerebrospinal fluid (CSF) biomarkers b-amyloid peptide of 42 amino acids (Ab 1-42), total tau-protein (T-tau) and tau phosphorylated at threonine 181 (P-tau 181P) are used to diagnose Alzheimer’s disease (AD). In order to increase diagnostic power, several biomarkers combinations have been proposed. In that sense Molinuevo et al. (1) developed a new CSF biomarker index, the AD-CSF index, which has been validated in clinically diagnosed AD patients using multi-analyte (Meso Scale Discovery) and single-analyte ELISA kits (Innogenetics) (2). This study validated the AD-CSF index in neuropathologically diagnosed AD patients, using both single-analyte (Innogenetics) and multi-analyte assays (Innogenetics). Methods: CSF of 51 neuropathologically diagnosed AD patients (3) and of 95 controls was analyzed by commercially available single-analyte ELISA-kits (INNOTEST, Innogenetics) and by a Research Use Only version of a multi-analyte Luminex assay (INNO-BIA AlzBio3, Innogenetics). Subsequently the AD-CSF indices were calculated. Results: Both T-tau and P-tau 181P AD-CSF indices were significantly increased in AD patients when compared to controls (p<0.001). The diagnostic power of the indices was calculated using ROC analyses, resulting in excellent sensitivity, specificity and accuracy values that systematically exceeded the 80% threshold, independent of the analytical platform used. Conclusions: The AD-CSF indices of both the ELISA and Luminex assays resulted in excellent accuracy values for discriminating neuropathologically confirmed AD patients from controls, independent of the analytical platform used. References Molinuevo JL, Gispert JD, et al. A new approach to the Alzheimer’s disease diagnosis with biomarkers: description of the AD-CSF-Index. Rev Neurol 2012;54(9):51322.Molinuevo JL, Gispert JD, et al. The AD-CSF-Index Discriminates Alzheimer’s Disease Patients from Healthy Controls: AValidation Study. JAlzheimers Dis 2013;36(1), 67-77.Le Bastard N, Coart E, et al. Comparison of two analytical platforms for the clinical qualification of Alzheimer’s disease biomarkers in pathologically-confirmed dementia. J Alzheimers Dis 2013;33(1):117-31.

LINKAGE ANALYSES OF EXTENDED CARIBBEAN HISPANIC FAMILIES INDICATES NOVEL LOCI ASSOCIATED WITH FAMILIAL LATE-ONSET ALZHEIMER'S DISEASE

phosphorylated at threonine 181 (P-tau 181P) were available for 204 patients. The effect of AAO and CSF biomarker profiles on the olfactory receptor CNV was assessed in a univariate analysis of variance. Results: The assay identified a CNV spanning 156 kb including the genes OR4M1, OR4N2, OR4K2, OR4K5 and OR4K. Only multiplications of this gene region where identified in AD patients, ranging from 2 to 5 copies. A significant difference in AAO was found between AD patients with a high (mean AAO 77.268.8 years) and a low olfactory receptor copy number (mean AAO 74.868.9; P1⁄40.02). Furthermore, CSF levels of Ab 1-42 were associated with a high olfactory receptor copy number in AD patients. Conclusions: Our data imply that AD patients with a low olfactory copy number have an earlier AAO of disease. These findings are in contrast with a previous published report, however we were able to identify an effect of the olfactory receptor CNV. The olfactory receptor cluster might potentially be a modifier locus of AAO in AD. Further studies can elucidate the impact of the olfactory receptor CNVand might play an important role in the early detection of disease.

Biomarcadores en líquido cefalorraquídeo de pacientes con enfermedad de Alzheimer prodrómica

Introduction: The prodromal Alzheimers disease (AD) is a new concept that include an amnesic mild cognitive impairment (MCI- a) and alterations in some complementary tests. Objective: To test the presence of alterations in the cerebrospinal fluid (CSF) bio- markers in our MCI-a patients who developed AD in the first year after the lumbar puncture. Method: 24 control subjects and 36 MCI-a patients were included from the local hospital memory cli- nic. Using INNO-BIA Alzbio-3 reagents from Innogenetics, we quantified CSF Aβ1-42, T-tau and P-tau181p proteins, and calcu- lated the ratios T-tau / Aβ1-42 y P-tau 181p / Aβ1-42. This project was approved by the local Ethical Committee. Results: One year after the lumbar puncture, 14 MCI patients (38%) developed AD. These patients showed lower Aβ1-42 protein levels (285.37 ± 73.36 vs. 365.21 ± 112.53 pg/ml, p < 0.02) and higher T-tau protein (88.3 ± 40.82 vs. 53.21 ± 23.38 pg/ml, p < 0.002), P-tau 181p protein (66.44 ± 23.87 vs. 31.25 ± 13.74 pg/ml, p< 0.02 ), T-tau / Aβ1-42 ratio (0.34 ± 0.19 vs. 0.15 ± 0.08, p < 0.001 ) and P-tau 181p / Aβ1-42 ratio (0.25 ± 0.12 vs. 0.09 ± 0.06, p < 0.0001) than the control subjects. Conclusion: In our experience, as the recent literature, it exist the very clear alterations of CSF biomarkers in patients with prodromal AD. (Alzheimer. Real Invest Demenc. 2011;49:19-25)

Improved discrimination of autopsy-confirmed Alzheimer's disease (AD) from non-AD dementias using CSF P-tau 181P

To establish diagnostic accuracy (acc) and optimal cut-off levels of CSF tau phosphorylated at threonine 181 (P-tau 181P) for discriminating Alzheimer's disease (AD) from non-AD dementias in autopsy-confirmed dementia patients, CSF levels of β-amyloid peptide (Aβ 1–42), total tau protein (T-tau) and P-tau 181P from patients with definite AD ( n = 95) and non-AD dementias ( n = 50) were determined with single-parameter ELISA kits. Optimal P-tau 181P cut-off levels for differentiating AD from pooled non-AD dementias, dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) were 50.4 pg/mL (acc = 0.73), 52.8 pg/mL (acc = 0.73) and 35.3 pg/mL (acc = 0.90), respectively. The optimal CSF P-tau 181P cut-off level for discriminating AD from non-AD dementias was 50.4 pg/mL. Optimal CSF P-tau 181P cut-off levels differed between non-AD diagnostic dementia categories.

P3-068: Improved discrimination of Alzheimer's disease from other dementias using cerebrospinal fluid P-tau 181P

P3-068: Improved discrimination of Alzheimer's disease from other dementias using cerebrospinal fluid P-tau 181P

P3-093: Characterization of CSF Aβ 1-42, Tau and p-Tau 181p concentrations at baseline in Alzheimer's disease neuroimaging initiative study patients

P3-093: Characterization of CSF Aβ 1-42, Tau and p-Tau 181p concentrations at baseline in Alzheimer's disease neuroimaging initiative study patients

P-057: Validation of the xMAP technology and performance of INNO-BIA AlzBio3 for quantification in CSF of Aβ 1-42, total tau and P-tau 181p

P-057: Validation of the xMAP technology and performance of INNO-BIA AlzBio3 for quantification in CSF of Aβ 1-42, total tau and P-tau 181p

Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia

To establish diagnostic performance of the cerebrospinal fluid (CSF) biomarkers β-amyloid peptide (Aβ 1–42), total tau-protein (T-tau) and tau phosphorylated at threonine 181 (P-tau 181P) compared to clinical diagnosis, biomarker levels were determined in CSF samples from 100 autopsy-confirmed dementia and 100 control subjects. As the control and dementia groups were not age-matched and given the significant associations of biomarker concentrations with age in controls, age-corrected biomarker concentrations were calculated. New models were constructed by means of logistic regression. Using all biomarkers, dementia could be discriminated from controls (sensitivity ( S) = 86%, specificity (Sp) = 89%). T-tau and Aβ 1–42 optimally discriminated Alzheimer's disease (AD) from other dementias (NONAD) and controls ( S = 90%, Sp = 89%). AD was optimally discriminated from NONAD using P-tau 181P and Aβ 1–42 ( S = 80%, Sp = 93%). Diagnostic accuracy of the latter model (82.7%) was comparable to clinical diagnostic accuracy (81.6%) that was based on a whole clinical work-up (including imaging). Using this model, in cases with clinically doubtful diagnoses, a correct diagnosis would have been established in 4/6 autopsy-confirmed AD and 3/3 autopsy-confirmed NONAD cases. The value of biomarkers in differential dementia diagnosis was shown, using pathological diagnosis as a reference. New models have been developed, achieving sensitivity, specificity and diagnostic accuracy levels, consistently exceeding 80%.

Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: A multicenter study

In this report we evaluated the clinical performance of APOE genotyping and three protein biomarkers (total tau, β-amyloid 1–42, and tau phosphorylated at threonine 181) in a prospective multicenter study using the INNO-BIA AlzBio3 assay applied on Luminex platform. Concentration of biomarkers of Alzheimer's disease in cerebrospinal fluid (CSF) was measured with multiplexing technology ( n = 223), and compared to the results of ELISA assays in patients with early dementias or mild cognitive impairment (MCI) collected at 12 gerontopsychiatric university departments, and APOE genotyping was performed. Concentrations of Aβ 1–42 were statistically significantly lower in MCI-AD subjects compared to MCI-O, and significantly lower in D-AD patients compared to MCI-O. P-tau 181P concentrations were significantly higher in MCI-AD patients compared to MCI-O, and significantly higher in D-AD patients compared to MCI-O. The total tau concentrations in MCI-AD patients were significantly higher compared to MCI-O, and higher in D-AD compared to MCI-O, moreover, the concentration of total tau was significantly higher in D-AD compared to MCI-AD patients. For the differential diagnosis between D-AD and D-O, the optimal cutoff concentration of Aβ 1–42 was 197.7 pg/mL, and that for P-tau 181P was 47.9 pg/mL. These cutoff values were also applied to discriminate between MCI-AD and MCI-O subjects. Simultaneous measurement of the biomarkers significantly improves management of the samples and quality control of the assays’ performance.

International quality control survey of neurochemical dementia diagnostics

Currently, neurochemical dementia diagnostics (NDD) are increasingly entering routine clinical neurochemistry, offering improved early and differential diagnosis of dementias. However, there is an obvious lack of standardization in pre-analytical sample handling and systematic quality surveys. Therefore, in this study, 14 laboratories in Germany, Austria, and Switzerland were given aliquots of a human cerebrospinal fluid (CSF) sample, and were asked to measure Alzheimer's disease (AD) biomarkers (amyloid β (Aβ) peptides, total Tau protein, and phosphorylated Tau protein (P-tau 181P)) according to their routine protocols. Results: The inter-laboratory coefficients of variation of the results obtained by the laboratories participating in this study were in the range of 20–30%. Although the results of this quality control survey are promising, the quality of measurements has to be further optimized.

AB 42 peptides, tau, and P-tau 181P as biomarkers for early diagnosis: A multiparametric approach using xMAP™ technology

AB 42 peptides, tau, and P-tau 181P as biomarkers for early diagnosis: A multiparametric approach using xMAP™ technology