|
|
Alzheimer`s & Dementia
Year: 2012 | Volume: 8 | Issue: 4 | Page No.: 250 - 260
|
 |
Improved protocol for measurement of plasma β-amyloid in longitudinal evaluation of Alzheimers Disease Neuroimaging Initiative study patients
|
Michal J. Figurski,
Teresa Waligorska,
Jon Toledo,
Hugo Vanderstichele,
Magdalena Korecka,
Virginia M.Y. Lee,
John Q. Trojanowski
and
Leslie M. Shaw
|
Abstract: Background
The interassay variability and inconsistency of plasma β-amyloid (Aβ) measurements among centers are major factors precluding the interpretation of results and a substantial obstacle in the meta-analysis across studies of this biomarker. The goal of this investigation was to address these problems by improving the performance of the bioanalytical method.
Methods
We used the Luminex immunoassay platform with a multiplex microsphere-based reagent kit from Innogenetics. A robotic pipetting system was used to perform crucial steps of the procedure. The performance of this method was evaluated using two kit control samples and two quality control plasma samples from volunteer donors, and by retesting previously assayed patient samples in each run. This setup was applied to process 2454 patient plasma samples from the Alzheimers Disease Neuroimaging Initiative study biofluid repository. We have additionally evaluated the correlations between our results and cerebrospinal fluid (CSF) biomarker data using mixed-effects modeling.
Results
The average precision values of the kit controls were 8.3% for Aβ1-40 and 4.0% for Aβ1-42, whereas the values for the plasma quality controls were 6.4% for Aβ1-40 and 4.8% for Aβ1-42. From the testretest evaluation, the average precision was 7.2% for Aβ1-40 and 4.5% for Aβ1-42. The range of final plasma results for Alzheimers Disease Neuroimaging Initiative patients was 13 to 372 pg/mL (median: 164 pg/mL) for Aβ1-40 and 3.5 to 103 pg/mL (median: 39.3 pg/mL) for Aβ1-42. We found that sample collection parameters (blood volume and time to freeze) have a small, but significant, influence on the result. No significant difference was found between plasma Aβ levels for patients with Alzheimers disease and healthy control subjects. We have determined multiple significant correlations of plasma Aβ1-42 levels with CSF biomarkers. The relatively strongest, although modest, correlation was found between plasma Aβ1-42 levels and CSF p-tau181/Aβ1-42 ratio in patients with mild cognitive impairment. Plasma Aβ1-40 correlations with CSF biomarkers were weaker and diminished completely when we used longitudinal data. No significant correlations were found for the plasma Aβ1-42/Aβ1-40 ratio.
Conclusions
The precision of our robotized method represents a substantial improvement over results reported in the literature. Multiple significant correlations between plasma and CSF biomarkers were found. Although these correlations are not strong enough to support the use of plasma Aβ measurement as a diagnostic screening test, plasma Aβ1-42 levels are well suited for use as a pharmacodynamic marker. |
View Fulltext
| Related
Articles | Back
|
|
|
|
|
|
|
|
Related
Articles |
No Article Found
|
|
|
|
|