December 12, 2022
Sysmex Corporation【Overview presentation】
15th Clinical Trials on Alzheimer’s Disease (CTAD)

Age dependency of plasma β-amyloid measured by fully automated andhighly specific immunoassays in a Japanese cohort study (SESSA)

Authors

Kengo Ishiki1, Moniruzzaman2, Yuichiro Yano2, Keiko Kondo2, Aya Kadota2), Masahiro
Miura1, Shigeki Iwanaga1, Masaki Nishimura3, Hirotsugu Ueshima2, Katsuyuki Miura2

1Central Research Laboratories, Sysmex Corporation
2NCD Epidemiology Research Center (NERC), Shiga University of Medical Science
3Molecular Neuroscience Research Center, Shiga University of Medical Science

Overview
presentation

Backgrounds
In recent years, blood-based plasma β-amyloid (Aβ) has been increasingly studied
as a potential biomarker of Alzheimer’s disease (AD) because it is less invasive, morecost-effective, and easily accessible. Mounting evidence shows that the ratio ofplasma Aβ1-42 to Aβ1-40 (Aβ42/Aβ40) is highly concordant with amyloid PET status,suggesting that it may reflect the brain Aβ pathology. Besides amyloid pathology inthe brain, other risk factors for AD development are known, most notably age.
Considering the use of plasma Aβ for the enrollment of subjects for clinical trials orfor diagnostic adjunct purposes, it is important to understand the association between
age and plasma Aβ. Because many disease-modifying therapies currently underdevelopment target the early stages before the onset of AD, it is necessary tounderstand the age dependency of plasma Aβ in older adults with normal cognitivefunction. However, several studies have reported conflicting results regarding the age
dependence of plasma Aβ levels.
Aβ is known to be unstable in the blood, and various factors at the time of bloodcollection are known to influence levels of blood Aβ. Such factors may influence thecontralateral results on age dependency so far. Currently, the technique of cancelingthe effect by taking the ratio as Aβ42/ Aβ40 is often used. On the other hand, whentrying to understand the age-dependency of Aβ40 and Aβ42 alone, the handling ofsamples during blood collection requires rigor.

Objectives
In this study, we aimed to examine the age-dependency of plasma Aβ40 and Aβ42
in a general Japanese male population using samples collected under a uniform
protocol.
Methods
The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) is an
ongoing epidemiological study in a general population randomly selected fromKusatsu City (Japan) residents at baseline (2006–2008). The second survey wasperformed between 2010 and 2014 and a total of 853 men aged 46–83 participatedin medical examination. We collected blood samples by venipuncture and stored themat -80 degrees Celsius until measurement. For sample collection, blood collected ina collection tube containing EDTA was mixed by gently inverting several times, thenstored on ice until centrifugation. Plasma Aβ40 and Aβ42 were measured using a fully
automated immunoassay platform (HISCLTM series) in 2021. Both Aβ40 and Aβ42
were measured twice, and the average was used for analysis. We evaluated the agedependency of Aβ40 and Aβ42 based on the measurement results of 822 participants,excluding 31 participants for whom measurements could not be performed. For thispurpose, we divided participants into 5 age groups at 10 years intervals and examined
the age dependency of Aβ40, Aβ42, and Aβ42/Aβ40 ratio by the Kruskal-Wallis test.

Results
The mean age of the participants was 69 years. There were significant differences
in both Aβ40 and Aβ42 across the age groups, but not for Aβ42/Aβ40 ratio. Thechange per year of age for Aβ40 and Aβ42 were showing a significant increase byage. On the other hand, the change per year of age for Aβ42/Aβ40 ratio was showing
a significant decrease by age.
Conclusion
Our results showed that plasma Aβ40 and Aβ42 increase in an age-dependent
manner, while the Aβ42/Aβ40 ratio decreases in an age-dependent manner. This agerelated change in plasma Aβ levels may be due to changes in production or functionalchanges in the blood-brain barrier. However, compared with the age-dependentchanges in Aβ40 and Aβ42, the age-dependency of Aβ42/Aβ40 ratio was more
gradual, with no significant differences found in the analysis divided into 5 age groups.
It may suggest that age dependence may be reduced by using the Aβ42/Aβ40 ratio.
Although the present results were based only on men and limited to the Japanesepopulation, they suggest that using appropriate sample handling protocols andmeasurement methods may be able to assess the relationship between plasma Aβand other factors. To further our understanding of plasma Aβ, an assessment of theassociation with cognitive function and other AD risk factors, as well as in women andother races, is warranted in the future.
SessionPoster, Clinical Trials: Biomarkers including plasma（LP68）