Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu; “Sysmex”) and Eisai Co., Ltd. (HQ: Tokyo, Japan; CEO: Haruo Naito; “Eisai”) are pursuing a joint project to develop a method of diagnosing Alzheimer’s disease (AD) using blood, presented two posters showing the most recent data from the project. The presentations took place at the 12th Clinical Trials on Alzheimer’s Disease (CTAD) conference, from December 4 to 7, 2019, in San Diego, California. At CTAD, Sysmex demonstrated on behalf of the two companies the possibility of understanding amyloid pathology in the brain from the brain-derived amyloid beta (Aβ) in plasma measured using its protein measurement platform, the HISCL™ series of fully automated immunoassay analyzers.
[Data sheet]
Blood diagnosis
P75
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Prediction of amyloid pathology by the plasma Aβ(1-42)/Aβ(1-40) ratio measured with a fully automated immunoassay system (HISCLTM series) Poster presentation: December 4 (Wed.) to December 5 (Thu.)
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In the presentation (P75), to create a simple blood diagnostic test for AD, the result of the receiver operating characteristic (ROC) analysis of the plasma Aβ1-42/Aβ1-40 ratio, measured using the HISCLTM series, was used as a prediction factor for Aβ-PET positivity. The HISCLTM system enables an automated immune assay to be completed in 17 minutes with sample volumes as small as 10-30µL, and it was demonstrated that the Aβ assay in plasma had sufficient sensitivity and high reliability. In addition, it was confirmed that the Aβ assay system using the HISCLTM series had a high correlation with IP-MS methods reported in Poster 81.
The samples from 192 persons living with the disease with mild cognitive impairment (MCI) and AD associated with amyloid PET results were used for investigation with the HISCLTM series. Using the plasma Aβ1-42/Aβ1-40 ratio, amyloid PET positivity can be predicted with a sensitivity of 73% and a specificity of 71% (AUC0.74), and it was confirmed that sensitivity and specificity were improved (AUC0.82) by adding factors such as age and APOE4, a gene associated with a greatly increased risk of developing AD. This preliminary result indicates the plasma Aβ1-42/Aβ1-40 ratio measured with the HISCLTM series could be used as a prescreening method for amyloid PET. To further assess its clinical utility, additional sample sets will be evaluated.
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Blood diagnosis
P81
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Clinical utility of plasma amyloid beta measurements by immunoaffinity enrichment and LC-MS/MS
Poster presentation: December 4 (Wed.) to December 5 (Thu.)
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In the presentation (P81), the development of high-sensitivity peptide (Aβ1-42 and Aβ1-40) measurement technology using mass spectrometry was described. With this technology, it is possible to measure the peptides in a liquid sample in two hours with a small sample volume of 250µL, and it was confirmed that the amounts of Aβ1-42 and Aβ1-40 in CSF and plasma could be measured. In addition to the presentation on the measurement performance (dynamic range, sensitivity, reproducibility, etc.) of this method under pure conditions, a good correlation between the CSF Aβ1-42/Aβ1-40 ratio and plasma Aβ1-42/Aβ1-40 ratio in elderly persons with normal cognition and those living with MCI and AD (44 people in total) was confirmed.
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1 | World Alzheimer Report 2018 |
2 | Promotion of Comprehensive Measures against Dementia, Ministry of Health, Labour and Welfare |
3 | Study on Economic Impact of Dementia in Japan, 2014 Health Labour Sciences Research Grant Annual Report |
4 | Estimated by Sysmex based on Japan’s Medium-term Economic Outlook (February 2018), Daiwa Institute of Research |
5 | Aβ, a peptide consisting of amino acid residues, is generated by excision from the amyloid precursor protein. Aβ1-40 consists of 40 residues, is the dominant substance, and does not fluctuate significantly as AD progresses. In contrast, Aβ1-42, which consists of 42 residues, has high aggregability and a reduction in Aβ1-42 is detected from the early stage of AD. There are individual differences in the absolute value of Aβ as well as intra-individual variabilities, therefore, it has been reported that there is a high correlation between the Aβ1-42/Aβ1-40 ratio in CSF and amyloid PET. |
6 | The correlation coefficient indicates the strength of the relationship between the two sets of data from the two quantitative data distributions. In this analysis, Spearman's rank correlation coefficient (rs), which is an index of correlation obtained from rank data, is calculated. |