Tau Protein Phosphorylated at Threonine 181 in CSF as a Neurochemical Biomarker in Alzheimer's Disease: Original Data and Review of the Literature

Lewczuk, Piotr; Esselmann, Hermann; Bibl, Mirko; Beck, Georg; Maler, Juan Manuel; Otto, Markus; Kornhuber, Johannes; Wiltfang, Jens

doi:10.1385/jmn:23:1-2:115

Cited by 105 publications

(67 citation statements)

References 46 publications

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“…The P-tau 181P /T-tau ratio can discriminate patients with Creutzfeldt-Jakob disease from those with other neurological disorders, including AD and FTD (26,27). 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).…”

Section: Bereitgestellt Von | Universitaetsbibliothek Der Lmu Muenchensupporting

confidence: 66%

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)

154

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: 66%

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)

154

102

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“…Abnormalities related to ␤-amyloid [11][12][13][14][15] and the protein Tau 16 -20 in the brain have been the subject of much greater focus, and these factors are thought to play a more central role in AD. [21][22][23][24][25][26][27] Yet, there continues to be support from various lines of clinical research for a link between AD and cerebral microvascular disease as well. 2,6,8,28 -36 Cerebrovascular abnormalities associated with AD have received only limited neuropathological consideration.…”

mentioning

confidence: 99%

Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and APOE Genotype

Stopa

Butala

Salloway

et al. 2008

Stroke

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Background and Purpose-We examined the associations among the vascular ␤-amyloid levels, smooth muscle actin, wall thickness, and lumen diameter to achieve greater understanding of the arteriolar changes that accompany Alzheimer disease (AD). Methods-Post-mortem pathology brain specimens from 76 patients with AD and 19 non-AD age control subjects were studied. We analyzed arterioles of the frontal cortex (Brodmann area 10) by immunohistochemistry and morphometry, and derived measures of vascular ␤-amyloid level, smooth muscle actin (SMA) volume, and arteriolar wall thickness and lumen diameter. APOE genotype was determined for each case. Results-Overall, there was a striking reciprocal relationship between arteriolar ␤-amyloid volume and smooth muscle actin (PϽ0.0001). In addition, there was a strong positive association between progressively accumulating vascular ␤-amyloid and augmentations in both wall thickness (PϽ0.0001) and lumen width (PϽ0.0001). In comparison with non-AD control subjects, smooth muscle actin was decreased in patients clinically diagnosed with AD and was reduced Ͼ10-fold in cases with AD pathology (Braak I to VI) compared with those lacking AD neuropathology. Significantly altered composition and structure of cortical vessels in pre-Braak stages corroborated our hypothesis that arterioles are devastated early in the AD pathological process. Smooth muscle actin, arteriolar wall thickness, and luminal diameter did not vary with Braak stage severity (PϾ0.05), indicating that substantial arteriolar damage may precede at least some of the interstitial plaques and neuronal tangles. Moreover, the structural and biochemical arteriolar abnormalities did not vary as a function of APOE genotype (PϾ0.05). Conclusion-We postulate that in elderly patients, the continually progressing ␤-amyloid-associated angiopathy, at the arteriolar level, harms the contractile apparatus and cerebral blood flow autoregulation, thereby making the downstream capillaries vulnerable to damage. Collectively, our observations lend further support to the idea that microvascular damage has a role, perhaps relatively early, in the onset of major AD pathology. (Stroke. 2008;39:814-821.)

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“…21,23 Briefly, with the assay of the Genetics Co. (Zü rich, Switzerland) Abx-42 peptide was measured, as the capturing antibody of this assay is not N terminus specific, and with the assay of Innogenetics (Ghent, Belgium), Ab1-42 peptide was measured, as the capturing antibody of this assay shows N terminus specificity. In both assays, the detecting antibodies are specific for the position 42.…”

Section: Assaysmentioning

confidence: 99%

Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study

et al. 2008

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In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins a and b (sAPPa and sAPPb) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examinationX20 in majority of cases) and mild cognitive impairment (MCI) in 12 gerontopsychiatric centers, and the clinical diagnoses were supported by neurochemical dementia diagnostic (NDD) tools: CSF amyloidb peptides, Tau and phospho-Tau. sAPPa and sAPPb were measured with multiplexing method based on electrochemiluminescence. sAPPa and sAPPb CSF concentrations correlated with each other with very high correlation ratio (R = 0.96, P < 0.001). We observed highly significantly increased sAPPa and sAPPb CSF concentrations in patients with NDD characteristic for Alzheimer's disease (AD) compared to those with NDD negative results. sAPPa and sAPPb highly significantly separated patients with AD, whose diagnosis was supported by NDD findings (sAPPa: cutoff, 117.4 ng ml À1 , sensitivity, 68%, specificity, 85%, P < 0.001; sAPPb: cutoff, 181.8 ng ml À1 , sensitivity, 75%, specificity, 85%, P < 0.001), from the patients clinically assessed as having other dementias and supported by NDD untypical for AD. We conclude sAPPa and sAPPb might be regarded as novel promising biomarkers supporting the clinical diagnosis of AD.

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Tau Protein Phosphorylated at Threonine 181 in CSF as a Neurochemical Biomarker in Alzheimer's Disease: Original Data and Review of the Literature

Cited by 105 publications

References 46 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

Cerebral Cortical Arteriolar Angiopathy, Vascular Beta-Amyloid, Smooth Muscle Actin, Braak Stage, and APOE Genotype

Soluble amyloid precursor proteins in the cerebrospinal fluid as novel potential biomarkers of Alzheimer's disease: a multicenter study

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