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

Abstract

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. 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. 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. 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.