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Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer's disease and down syndrome.
- Source :
-
Molecular neurodegeneration [Mol Neurodegener] 2017 Sep 04; Vol. 12 (1), pp. 63. Date of Electronic Publication: 2017 Sep 04. - Publication Year :
- 2017
-
Abstract
- Background: There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD.<br />Methods: We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts.<br />Results: In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 ± 0.166 pg/ml in AD versus 0.0405 ± 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 ± 1.26 pg/ml in DS versus 0.0415 ± 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R <superscript>2</superscript>  = 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R <superscript>2</superscript>  = 0.4525, p = 0.023).<br />Conclusions: We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled studies to validate the usefulness of plasma p-tau181 as an urgently needed surrogate marker for the diagnosis and disease progression of AD.
- Subjects :
- Aged
Aged, 80 and over
Alzheimer Disease blood
Alzheimer Disease pathology
Amyloid beta-Peptides blood
Case-Control Studies
Down Syndrome blood
Down Syndrome pathology
Female
Humans
Male
Phosphorylation
Pilot Projects
Alzheimer Disease diagnosis
Biomarkers blood
Brain metabolism
Down Syndrome diagnosis
tau Proteins blood
Subjects
Details
- Language :
- English
- ISSN :
- 1750-1326
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular neurodegeneration
- Publication Type :
- Academic Journal
- Accession number :
- 28866979
- Full Text :
- https://doi.org/10.1186/s13024-017-0206-8