CSF biomarkers for early-onset Alzheimer's disease in Chinese population from PUMCH dementia cohort

Dan Lei; Chenhui Mao; Jie Li; Xinying Huang; Longze Sha; Caiyan Liu; Liling Dong; Qi Xu; Jing Gao

doi:10.3389/fneur.2022.1030019

CSF biomarkers for early-onset Alzheimer's disease in Chinese population from PUMCH dementia cohort

Front Neurol. 2023 Jan 9:13:1030019. doi: 10.3389/fneur.2022.1030019. eCollection 2022.

Authors

Dan Lei¹, Chenhui Mao¹, Jie Li¹, Xinying Huang¹, Longze Sha², Caiyan Liu¹, Liling Dong¹, Qi Xu², Jing Gao¹

Affiliations

¹ State Key Laboratory of Complex Severe and Rare Diseases, Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
² State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Introduction: Alzheimer's disease (AD) is one of the highly concerned degenerative disorders in recent decades. Though vast amount of researches has been done in various aspects, early-onset subtype, however, needs more investigation in diagnosis for its atypical manifestations and progression process. Fundamental CSF biomarkers of early-onset AD are explored in PUMCH dementia cohort to depict its laboratory characteristics.

Materials and methods: A total of 125 individuals (age of onset <65 years old) from PUMCH dementia cohort were recruited consecutively and classified into AD, non-AD dementia, and control groups. Levels of amyloid-β 42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) were measured using ELISA INNOTEST (Fujirebio, Ghent, Belgium). Students' t-test or non-parametric test are used to evaluate the differences between groups. Area under curve (AUC) of receiver operating characteristic (ROC) curve was introduced to prove the diagnostic powers of corresponding markers. Logistic regression is used to establish diagnostic model to combine several markers together to promote the diagnostic power.

Results: The average of all three biomarkers and two calculated ratios (t-tau/Aβ42, p-tau/Aβ42) were statistically different in the AD group compared with the other two groups (Ps < 0.01). From our data, we were able to provide cutoff values (Aβ42 < 570.9 pg/mL; p-tau > 56.49 pg/mL; t-tau > 241.6 pg/mL; t-tau/Aβ42 > 0.529; p-tau/Aβ42 > 0.0846) with acceptable diagnostic accuracy compared to other studies. Using a combination of biomarkers and logistic regression (area under curve 0.951), we were able to further improve diagnostic efficacy.

Discussion: Our study supports the diagnostic usefulness of biomarkers and defined cutoff values to diagnose early-onset AD. We showed that the ratios of t-tau/Aβ42 and p-tau/Aβ42 are more sensitive than relying on Aβ42 levels alone, and that we can further improve diagnostic accuracy by combining biomarkers.

Keywords: Alzheimer's disease; CSF biomarkers; combination; cutoff value; early-onset.

Grants and funding

This work was supported by the National Key Research and Development Program (Grant Nos. 2020YFA0804500 and 2020YFA0804501), CAMS Innovation Fund for Medical Sciences (Grant Nos. 2020-I2M-C&T-B-010 and 2021-I2M-1-020), and the National Natural Science Foundation of China (Grant Nos. 81550021 and 30470618).