Amyloid β(1–42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease

Schoonenboom, Niki S.M.; Pijnenburg, Yolande A.L.; Mulder, Cees; Rosso, Sonia M.; Elk, Evert J. van; Kamp, Gerard J. van; Swieten, John van; Scheltens, Philip

doi:10.1212/01.wnl.0000123249.58898.e0

Cited by 174 publications

(116 citation statements)

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“…Similar cutoff values were published for discrimination of AD patients from controls by Lewczuk et al (28). Higher diagnostic accuracy was reported for the combination of low CSF Ab 1-42 and high P-tau 181P in differentiating early-onset AD from FTD (6) and for differentiation of AD and healthy controls (29). Identical results with respect to Ab 1-42 and T-tau for comparison between CS, AD, and DLB have been published recently (30).…”

Section: Bereitgestellt Von | Universitaetsbibliothek Der Lmu Muenchensupporting

confidence: 67%

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Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Vanderstichele¹,

Vreese²,

Blennow³

et al. 2006

Clinical Chemistry and Laboratory Medicine (CCLM)

156

102

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Background: Total tau (T-tau) and b-amyloid (Ab 1-42 ) levels in cerebrospinal fluid (CSF) can differentiate Alzheimer's disease (AD) from normal aging or depressive pseudo-dementia. Differential diagnosis from dementia with Lewy bodies (DLB) in clinical settings is difficult. Methods: The analytical performance of the INNO-TEST ᮋ PHOSPHO-TAU (181P) assay was validated in terms of selectivity, sensitivity, specificity, precision, robustness, and stability. Clinical utility of the assay alone, or combined with T-tau and Ab 1-42 , for discrimination of AD (ns94) from patients suffering from DLB (ns60) or from age-matched control subjects (CS) (ns60) was assessed in a multicenter study. Results: CSF concentrations of tau phosphorylated at threonine 181 (P-tau 181P ) in AD was significantly higher than in DLB and CS. Discriminant analysis, a classification tree, and logistic regression showed that P-tau 181P was the most statistically significant single variable of the three biomarkers for discrimination between AD and DLB. Conclusions: P-tau 181P quantification is a robust and reliable assay that may be useful in discriminating AD from DLB.

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Section: Bereitgestellt Von | Universitaetsbibliothek Der Lmu Muenchensupporting

confidence: 67%

“…Since distinction of AD from DLB is difficult in clinical settings, but important for patient management, as the treatment strategies are different, P-tau 181P determination may prove to be of clinical value. In addition, combined measurement of b-amyloid (Ab ) and P-tau 181P levels has been shown to differentiate AD from FTD (6).…”

Section: Introductionmentioning

confidence: 99%

Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Vanderstichele¹,

Vreese²,

Blennow³

et al. 2006

Clinical Chemistry and Laboratory Medicine (CCLM)

156

102

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“…These CSF-based assays are increasingly being supplemented with imaging biomarkers reflecting molecular pathology in vivo. Following the initial description of 11 C Pittsburgh compound B (PiB), 1 PET-based measures of amyloid pathology have come into increasing use in research and clinical settings. Several groups have demonstrated that PET measures of amyloid burden correlate well with CSF Ab42 measurements, and can be used in concert with other biomarkers as predictors of impending cognitive decline.…”

mentioning

confidence: 99%

“…[2][3][4] More recently, several promising PET radioligands for in vivo imaging of pathologic deposits of tau have been described. [5][6][7][8] As postmortem neurofibrillary tangle (NFT) burden is a predictor of global cognition 9 and CSF t-tau 10 and p-tau 11 improve the sensitivity and specificity of CSF Ab42 alone to identify those likely to progress to AD dementia, 2 in vivo imaging of tau pathology may represent a useful biomarker in clinical and translational AD research. 18 F-T807 (T807, also known as 18 F AV1451) is a radioligand with high selectivity for pathologic tau aggregates (especially NFT pathology 5,12 ) over amyloid plaques, limited nonspecific white and gray matter binding, 5 and circumscribed off-target binding.…”

mentioning

confidence: 99%

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

et al. 2016

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Objective: To better understand cross-sectional relationships between CSF and PET measures of tau pathology, we compared regional and global measures of 18 F-T807 (AV-1451) PET to CSF protein levels of total tau (t-tau), phosphorylated tau (p-tau), and b-amyloid 1-42 (Ab42).Methods: T-tau, p-tau, and Ab42 levels were assessed using INNOTEST xMAP immunoassays.Linear regression was used to compare regional and global measures of 18 F-T807 standardized uptake value ratios (SUVR) to CSF protein levels using data from 31 cognitively unimpaired elderly participants in the Harvard Aging Brain study.Results: After controlling for sex and age, total cortical 18 F-T807 binding was significantly correlated with p-tau (partial r 5 0.48; p , 0.01) and at trend level with t-tau (partial r 5 0.30; p 5 0.12). Regional 18 F-T807 measures were more strongly correlated with CSF protein levels than the global measure, with both t-tau and p-tau significantly correlated with 18 F-T807 SUVR in entorhinal, parahippocampal, and inferior temporal cortical regions (partial r 5 0.53-0.73). Peak correlations between CSF and PET measures of tau were similar to those between CSF and PET measures of amyloid burden. Finally, we observed significantly higher temporal T807 SUVR in individuals with high amyloid burden.Conclusions: These data support the link between 18 F-T807 PET and CSF measures of tau pathology. In these cognitively normal individuals with 18 F-T807 binding largely restricted to the temporal lobe, 18 F-T807 SUVR in temporal regions appeared more reflective of CSF t-tau and p-tau than a total cortical measure. Neurology ® 2016;87:920-926 GLOSSARY Ab 5 b-amyloid; Ab42 5 b-amyloid 1-42; AD 5 Alzheimer disease; ADNI 5 Alzheimer's Disease Neuroimaging Initiative; CNE 5 cognitively normal elderly; DVR 5 distribution volume ratio; FLR 5 frontal, parietal, retrosplenial, and lateral temporal cortical regions; HAB 5 Harvard Aging Brain; ITC 5 inferior temporal neocortex; MCI 5 mild cognitive impairment; MGH 5 Massachusetts General Hospital; MMSE 5 Mini-Mental State Examination; MTC 5 middle temporal neocortex; NFT 5 neurofibrillary tangle; p-tau 5 phosphorylated tau; PiB 5 Pittsburgh compound B; ROI 5 region of interest; SUVR 5 standardized uptake value ratio; t-tau 5 total tau.Accumulations of b-amyloid (Ab) and intracellular tau are defining characteristics of Alzheimer disease (AD) pathology. CSF assays of Ab 1-42 (Ab42), total tau (t-tau), and tau phosphorylated at residue 181 (p-tau) proteins are commonly used tools for identifying individuals harboring AD pathology. These CSF-based assays are increasingly being supplemented with imaging biomarkers reflecting molecular pathology in vivo. Following the initial description of 11 C Pittsburgh compound B (PiB), 1 PET-based measures of amyloid pathology have come into increasing use in research and clinical settings. Several groups have demonstrated that PET measures of amyloid burden correlate well with CSF Ab42 measurements, and can be used in concert with other biomarkers as p...

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“…Det ble funnet statistisk signifikant høyere konsentrasjoner hos pasienter med Alzheimers sykdom i alle studiene (15, 24, 29 -34 Når det gjaldt p-tau, var det én studie der det ikke var statistisk signifikant forskjell mellom p-tau 181-nivå hos pasienter med Alzheimers sykdom og hos pasienter med frontotemporallappsdemens (29) -i fem andre studier hvor p-tau 181 var undersøkt, fant man høyere konsentrasjoner hos dem med Alzheimers sykdom enn hos dem med frontotemporallappsdemens (24,28,31,33,34). Sensitivitet og spesifisitet for evnen til p-tau 181 til å skille gruppene, var rapportert i fem studier (20,24,28,31,34) (fig 4, tab 2, e-tab 5).…”

Section: Alzheimers Sykdom Og Frontotemporallappsdemensunclassified

Biomarkører i spinalvæske ved demens

Skogseth¹,

Fladby²,

Mulugeta³

et al. 2011

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Amyloid β(1–42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease

Abstract: The combination of CSF Abeta42 and CSF Ptau-181 may help in differentiating EAD from FTLD.

Cited by 174 publications

References 38 publications

Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Analytical performance and clinical utility of the INNOTEST® PHOSPHO-TAU(181P) assay for discrimination between Alzheimer's disease and dementia with Lewy bodies

Temporal T807 binding correlates with CSF tau and phospho-tau in normal elderly

Biomarkører i spinalvæske ved demens

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