November 9, 2020
Sysmex Corporation
Eisai Co., Ltd.

Sysmex Presents Academic Report with a View to Creating a Simple
Method of Diagnosing Alzheimer’s Disease Using Blood- The Content Presented at the 13th Clinical Trials on Alzheimer’s Disease (CTAD) Conference -Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu; "Sysmex") and Eisai
Co., Ltd. (HQ: Tokyo, Japan; CEO: Haruto Naito; "Eisai") announced that the most recent data fromthe project to develop a method of diagnosing Alzheimer’s disease (AD) using blood plasma waspresented at the 13th Clinical Trials on Alzheimer's Disease (CTAD) conference, held virtually from
November 4 to 7, 2020. Sysmex demonstrated on behalf of the two companies the performance of
the amyloid beta (Aβ) in plasma measured on Sysmex's HISCLTM fully automated immunoassay
analyzers in predicting amyloid pathology as defined by amyloid positron emission tomography (PET)
imaging on the centiloid scale.1

Clinical trials:
Plasma Aβ ratio measured on a fully automated immunoassay
biomarkers including
predicts amyloid positivity defined by amyloid PET centiloidplasma
Poster presentation: November 4 (Wed.) to November 7 (Sat.)
LP10Our group has hitherto used the visual read method2, which is commonly used for clinical trials, toconfirm amyloid pathology by amyloid PET scan. Meanwhile, an increasing number of recent
research projects quantify amyloid PET images with the index called SUVR (Standard Uptake
Value Ratio) and correct with a standardized technique called the centiloid method to assess
amyloid pathology quantitatively.3 Accordingly, to assess the performance of the plasma Aβ1-42/Aβ140 (Aβ ratio) as measured on a fully automated immunoassay system HISCL in predicting amyloid
pathology, we used both the visual read method and centiloid method to determine amyloid
pathology for 149 cases clinically diagnosed as having MCI (Mild Cognitive Impairment) and mild
AD to ascertain the difference in their predictive performance.
The results confirmed that the centiloid method exhibited a better performance in determining
amyloid pathology with sensitivity and specificity measuring at 78% (AUC = 0.82), whereas
sensitivity and specificity was 72% and 71% (AUC = 0.74), respectively, for the visual read method.
Also, a correlation (Spearman’s rank correlation coefficient (rs)4 = -0.57, p < 0.0001) wasdetermined between the plasma Aβ ratio and the centiloid values, indicating more strongly thanever the potential to predict amyloid pathology in the brain with the plasma Aβ ratio. Furthermore,
it was observed that many instances where there was a mismatch between the decisions by theplasma Aβ ratio and the centiloid method were false-positive cases (positive by the plasma Aβratio, negative by amyloid PET centiloid). Other research groups have also reported on suchmismatches, suggesting that these false-positive subjects are more likely to test positive in amyloid
PET imaging than the negative subjects.5 It follows from these findings that there is a possibility
that the plasma Aβ ratio measured on a fully automated immunoassay system HISCL reflects
earlier amyloid pathology in the brain, which amyloid PET imaging cannot detect.
To further assess clinical utility of our assay system, we will evaluate additional sample sets.

The total number of those living with dementia across the world is projected to reach 82 million in
2030 and 152 million in 2050, with the total global societal cost of dementia stemming from direct
medical and social care costs and lower productivity being estimated to reach 2 trillion USD in 2030.6
In Japan, the number of those with dementia is thought to have reached approximately 4.62 million
in 2012 and is projected to grow to 7.30 million in 20257, with the total societal cost of this disease
being estimated to be equivalent to 4.1%8 of the gross domestic product (GDP) in 2025 (25.8 trillion
yen9). Of these sufferers, those living with AD are thought to account for more than 60% of thoseliving with dementia.7
It is conceivable that AD is a disease that results in synaptic dysfunction and neuronal cell death due
to tau deposition in neurons triggered by Aβ aggregation on the outside of neurons. These brainchanges cause cognitive impairment and psychological and behavioral symptoms, suggesting that
the Aβ aggregation and accumulation inside the brain is caused by AD before the presence ofcognitive impairment appears, thus, it is believed that early diagnosis and early intervention is moreeffective in therapies targeting Aβ. Currently, amyloid PET and Aβ ratio in cerebrospinal fluid (CSF)
are used for detecting amyloid aggregates in the brain, but this puts significant burden on patients interms of access, costs, and their physical wellbeing.10
Sysmex and Eisai are working to create new diagnostic technologies for the prevention and treatmentof dementia. Accordingly, the overarching aim is to contribute to the advancement of healthcare andimprove the quality of life for those living with the disease and their families.

Terminology
1 A standardization scale for integration analysis of PET SUVR values as measured bydifferent amyloid PET imaging probes.
2 Trained doctors qualitatively distinguish amyloid PET positive from amyloid negative
subjects by visually reading images.
3 Klunk WE et al, Alzheimer’s Dementia (2014)
4 Assesses how correlated two sets of data are based on two quantitative data distributions.
For the purpose of this analysis, Spearman's rank correlation coefficient (rs), which is acorrelation index as determined by the rankings of the two variables, was calculated.
5 Schindler SE et al, Neurology (2019)
6 World Alzheimer Report 2018
7 Promotion of Comprehensive Measures against Dementia, Ministry of Health, Labour andWelfare
8 Study on Economic Impact of Dementia in Japan, 2014 Health Labour Sciences Research
Grant Annual Report
9 Estimated by Sysmex based on Japan’s Medium-term Economic Outlook (February 2018),
Daiwa Institute of Research
10 Aβ is a peptide made of amino-acid residues removed from amyloid precursor protein. Manyof them are Aβ1-40, which is comprised of 40-residues, and the Aβ1-40 level does not fluctuatesignificantly as AD progresses. Comprised of 42-residues, Aβ1-42, on the other hand, ishighly cohesive and decreases in cerebrospinal fluid (CSF) from the early stages of AD. It
is believed that Aβ's absolute values show individual and intrinsic variability but that theplasma Aβ1-42/Aβ1-40 ratio remains unchanged. It has also been reported that the plasma
Aβ1-42/Aβ1-40 ratio in CSF shows a high correlation with amyloid PET.

About the collaboration between Sysmex and Eisai
In February 2016, Sysmex and Eisai signed a comprehensive non-exclusive agreement aimed at thedevelopment of new diagnostic tests in the field of dementia. By leveraging each other’s technologies
and knowledge, the objective has been to discover next-generation diagnostic reagents that will
enable early diagnosis of dementia, selection of the most appropriate treatment options, and regularmonitoring of the effects of such treatments. At the 12th CTAD held in December 2019, the twocompanies reported on the performance of the plasma Aβ ratio measured on a fully automatedimmunoassay system HISCL in predicting the amyloid PET scan results (sensitivity: 73%, specificity:
71% [AUC = 0.74]), thus demonstrating the potential to predict amyloid pathology in the brain using
the plasma Aβ ratio.* This finding was expected to lead to the development of a simple method of
diagnosing Alzheimer's disease using blood.
*

https://www.sysmex.co.jp/en/news/2019/191209.html
https://www.eisai.com/news/2019/news201990.html

Information contained in the press release is current as of the date of the announcement but may be subject to change without prior notice.