👤 Vladimir A Mitkevich

Early recognition of a risk of Alzheimer's disease (AD) remains a global challenge, and blood proteomic markers are of particular interest for wide-scale diagnostic use. Quantitative multiple reaction monitoring (MRM) approach demonstrates good reproducibility in the characteristic changes in the levels of reported candidate biomarkers (CBs) in different cohorts in AD. Following up on our previous study, we performed a joint analysis of 331 blood plasma samples from two different clinical cohorts of participants, comprising a total of 95 samples from patients with AD, 136 samples from patients with mild cognitive impairment (MCI), and 100 samples from controls. The obtained results confirm the significance of 37 CBs. A logistic regression-based algorithm was used to build protein classifiers, and a total of 21 important proteins were selected, 13 of which (ORM1, APOA4, LBP, HP, FN1, BCHE, APOE, PZP, A1BG, TF, SERPINA7, TTR, and F12) formed a universal panel that demonstrated strong classification performance in distinguishing AD patients from controls (ROC-AUC = 0.90) and in separating stable and progressing patients with MCI (ROC-AUC = 0.81). Overall, the analysis confirms the high potential of the MRM method for validating CBs in independent cohorts. Show less

The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer's disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels. Show less