Plasma amyloid-β oligomerization assay as a pre-screening test for amyloid status

Alzheimer’s Research & Therapy

Pieter Jelle Visser¹  Jori Tomassen¹  Philip Scheltens¹  Wiesje M. van der Flier¹  Seong Soo A. An²  Young Chul Youn³  SangYun Kim⁴  Bart N. M. van Berckel⁵  Sungmin Kang⁶  Charlotte E. Teunissen⁷  Rosha Babapour Mofrad⁷ 

[1] Alzheimer Center & Department of Neurology Amsterdam, Neuroscience Campus Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Vrije Universiteit Amsterdam;Department of Bionanotechnology, Gachon University;Department of Neurology, Chung-Ang University College of Medicine;Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine;Department of Radiology & Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC;Department of Research and Development, PeopleBio Inc;Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC;

关键词: Blood-based biomarker;    Plasma Aβ oligomer;    Amyloid status;    Multimer detection system;    Long-term storage;   

DOI  :  10.1186/s13195-021-00873-w

来源: DOAJ

【 摘 要 】

Abstract Objective We assessed the performance of plasma amyloid oligomerization tendency (OAβ) as a marker for abnormal amyloid status. Additionally, we examined long-term storage effects on plasma OAβ. Methods We included 399 subjects regardless of clinical diagnosis from the Amsterdam Dementia Cohort and European Medical Information Framework for AD project (age, 63.8 ± 6.6; 44% female). Amyloid status was determined by visual read on positron emission tomography (PET; nabnormal = 206). Plasma OAβ was measured using the multimer detection system (MDS). Long-term storage effects on MDS-OAβ were assessed using general linear models. Associations between plasma MDS-OAβ and Aβ-PET status were assessed using logistic regression and receiver operating characteristics analyses. Correlations between plasma MDS-OAβ and CSF biomarker levels were evaluated using Pearson correlation analyses. Results MDS-OAβ was higher in individuals with abnormal amyloid, and it identified abnormal Aβ-PET with an area under the curve (AUC) of 0.74 (95% CI, 0.67–0.81), especially in samples with a storage duration < 4 years. Combining APOEe4 and age with plasma MDS-OAβ revealed an AUC of 81% for abnormal amyloid PET status (95% CI, 74–87%). Plasma MDS-OAβ correlated negatively with MMSE (r = − 0.29, p < .01) and CSF Aβ42 (r = − 0.20, p < 0.05) and positively with CSF Tau (r = 0.20, p = 0.01). Conclusions Plasma MDS-OAβ combined with APOEe4 and age accurately identifies brain amyloidosis in a large Aβ-confirmed population. Using plasma MDS-OAβ as a screener reduced the costs and number of PET scans needed to screen for amyloidosis, which is relevant for clinical trials. Additionally, plasma MDS-OAβ levels appeared affected by long-term storage duration, which could be of interest for others measuring plasma Aβ biomarkers.

【 授权许可】

Unknown