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Plasma Oligomer β-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition

  • Original Research
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Abstract

Background

Multimer detection system-oligomeric amyloid-β (MDS-OAβ) measure plasma OAβ level, which is associated with earlier Alzheimer’s disease (AD) pathology. However, no study has investigated MDS-OAβ differences in cognitive normal older adults (CN) with or without cerebral Aβ burden and its correlation with Aβ deposition and white matter (WM) integrity.

Objective

To investigate associations among cerebral Aβ burden, MDS-OAβ, and WM integrity in CN.

Design

This is a single center, cross-sectional study which used data from Catholic Aging Brain Imaging (CABI) database.

Setting

CABI database contains brain scans of patients who visited the outpatient clinic at Catholic Brain Health Center, Yeouido St. Mary’s Hospital, The Catholic University of Korea, between 2017 and 2022.

Participants

A total 34 amyloid-PET negative CN and 23 amyloid-PET positive CN were included.

Measurements

Plasma Aβ level using MDS-OAβ, cerebral Aβ deposition level using global standardized uptake value ratio (SUVR) values, WM integrity using fractional anisotropy (FA) and mean diffusivity (MD), and cortical thickness from structural MRI were utilized.

Restuls

The amyloid-PET positive group showed higher MDS-OAβ level than the amyloid-PET negative group (0.997 ± 0.19 vs. 0.79 ± 0.28, P <0.005), but they did not differ in WM integrity or cortical thickness. The MDS-OAβ positive group showed higher global cerebral Aβ deposition or mean global SUVR values (0.609 ± 0.135 vs. 0.533 ± 0.121 vs. P <0.05), lower regional FA of left forceps minor and the right superior longitudinal fasciculus (family-wise error rate, p <0.05), and lower cortical thickness of left fusiform (p <0.05, Monte Carlo simulation) than the MDS-OAβ negative group. MDS-OAβ was positively associated with global cerebral Aβ deposition (r=0.278, P <0.05) and negatively associated (r = − 0.324, P < 0.05) with regional WM integrity.

Conclusions

In this study, MDS-OAβ value demonstrated earlier and different AD pathology than cerebral Aβ retention according to amyloid-PET. Longitudinal studies are needed to elucidate the causal relationships of plasma OAβ and cerebral Aβ with WM integrity disturbance and cortical atrophy during the AD trajectory.

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Acknowledgement

We thank So Jung Kim, a researcher of the Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, for her help in acquisition of blood samples.

Funding

Funding: This research was funded by Peoplebio inc. This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MIST) (No. 2022R1A2C109321512) and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number: HU22C0011). The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.

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Authors and Affiliations

  1. Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul, Korea

    S.-M. Wang, S.-H. Kim & Hyun Kook Lim

  2. Department of Psychiatry, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

    D. W. Kang & C. U. Lee

  3. Department of Psychiatry, St. Vincent Hospital, Suwon, Korea, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Y. H. Um

  4. Alzheimer Center & Department of Neurology Amsterdam, Neuroscience, Campus Amsterdam Neuroscience, VU University Medical Center, Amsterdam, UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

    P. Scheltens

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Contributions

Authors’ contributions: Author Hyun Kook Lim had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Sheng-Min Wang and Hyun Kook Lim drafted the manuscript and contributed to project design, data collection, management, analysis, and interpretation. Yoo Hyun Um and Dong Woo Kang contributed to project design, data collection, and management. Chang Uk Lee and Philip Scheltens contributed to data management and revision of the manuscript.

Corresponding author

Correspondence to Hyun Kook Lim.

Ethics declarations

Conflict of interest disclosure: Dr Scheltens is a full-time employee of EQT Life Sciences (formerly LSP) and Professor Emeritus at Amsterdam University Medical Centers. He has received consultancy fees (paid to the university) from Alzheon, Brainstorm Cell and Green Valley. Within his university affiliation he is global PI of the phase 1b study of AC Immune, Phase 2b study with FUJI-film/Toyama, phase 2 study of UCB and co-chair of the phase 3 study with NOVO-Nordisk. Until November 2022 he acted as chair of the EU steering committee of the phase 2b program of Vivoryon and the phase 2b study of Novartis Cardiology.

Ethical standards: The study was conducted in accordance with ethical and safety guidelines set forth by the Institutional Review Board of Yeouido St. Mary’s Hospital, The Catholic University of Korea (IRB number: SC18TNSI0063). All subjects provided written informed consent.

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Wang, SM., Kang, D.W., Um, Y.H. et al. Plasma Oligomer β-Amyloid and White Matter Microstructural Integrity in Cognitively Normal Older Adults According to Cerebral Amyloid Deposition. J Prev Alzheimers Dis 10, 837–846 (2023). https://doi.org/10.14283/jpad.2023.87

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