Objective To investigate the relationships of cerebrospinal fluid levels of collagen triple helix repeat containing-1 (CTHRC1) and olfactomedin-3 (OLFM3) with cognitive impairment and cerebrospinal fluid biomarker levels in patients with Alzheimer′s disease (AD).

Methods Ninety-six patients with AD were selected as study objects (AD group), and divided into mild group (n=34), moderate group (n=39) and severe group (n=33) according to Clinical Deentia Scale (CDR) score. Sixty patients without cognitive impairment who underwent lumbar puncture during the same period served as the control group. Enzyme-linked immunosorbent assays were used to measure cerebrospinal fluid levels of CTHRC1, OLFM3 and biomarkers β-amyloid (Aβ)-40, Aβ-42, Aβ42/Aβ-40, total tau (T-tau) and phosphorylated tau (P-tau). Cognitive impairment in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The relationships of CSF CTHRC1 and OLFM3 levels with cognitive impairment and cerebrospinal fluid biomarkers were analyzed.

Results The AD group showed significantly higher cerebrospinal fluid levels of CTHRC1, T-tau and P-tau, and significantly lower levels of OLFM3, Aβ-42 and Aβ42/Aβ-40 compared to the control group (P < 0.05). The area under the curve (AUC) for diagnosing AD with cerebrospinal fluid CTHRC1 and OLFM3 was 0.839 and 0.822, respectively, and the combined AUC was 0.923. Cerebrospinal fluid CTHRC1 of mild group, moderate group and severe group were increased successively, and OLFM3 was decreased successively, the difference was statistically significant (P < 0.05). Cerebrospinal fluid Aβ-42 and Aβ-42/Aβ-40 in mild, moderate and severe groups were decreased successively, while T-tau and P-tau were increased successively, with statistical significance (P < 0.05). The MMSE and MoCA scores of mild group, moderate group and severe group decreased successively, and the difference was statistically significant (P < 0.05). Cerebrospinal fluid CTHRC1 levels were positively correlated with disease severity, while OLFM3 levels were negatively correlated (P < 0.05). Cerebrospinal fluid CTHRC1 was negatively correlated with Aβ-42, Aβ42/Aβ-40, MMSE scores and MoCA scores, and positively correlated with T-tau and P-tau (P < 0.05). Cerebrospinal fluid OLFM3 was positively correlated with Aβ-42, Aβ42/Aβ-40, MMSE scores and MoCA scores, and negatively correlated with T-tau and P-tau (P < 0.05).

Conclusion In the cerebrospinal fluid of patients with AD, CTHRC1 is elevated while OLFM3 is decreased. Both CTHRC1 and OLFM3 are associated with the severity of AD, cognitive impairment and levels of cerebrospinal fluid biomarkers.