CSF-Targeted Proteomics Indicate Amyloid-Beta Ratios in Patients with Alzheimer's Dementia Spectrum

Abstract

BACKGROUND: According to recent studies, amyloid-beta (Abeta) isoforms as cerebrospinal fluid (CSF) biomarkers have remarkable predictive value for cognitive decline in the early stages of Alzheimer's disease (AD). Herein, we aimed to investigate the correlations between several targeted proteomics in CSF samples with Abeta ratios and cognitive scores in patients in AD spectrum to search for potential early diagnostic utility. METHODS: A total of 719 participants were found eligible for inclusion. Patients were then categorized into cognitively normal (CN), mild cognitive impairment (MCI), and AD and underwent an assessment of Abeta and proteomics. Clinical Dementia Rating (CDR), Alzheimer's Disease Assessment Scale (ADAS), and Mini Mental State Exam (MMSE) were used for further cognitive assessment. The Abeta42, Abeta42/Abeta40, and Abeta42/38 ratios were considered as means of comparison to identify those peptides corresponding significantly to these established biomarkers and cognitive scores. The diagnostic utility of the IASNTQSR, VAELEDEK, VVSSIEQK, GDSVVYGLR, EPVAGDAVPGPK, and QETLPSK was assessed. RESULTS: All investigated peptides corresponded significantly to Abeta42 in controls. In those with MCI, VAELEDEK and EPVAGDAVPGPK were significantly correlated with Abeta42 (p value < 0.001). Additionally, IASNTQSR, VVSSIEQK, GDSVVYGLR, and QETLPSK were significantly correlated with Abeta42/Abeta40 and Abeta42/38 (p value < 0.001) in this group. This group of peptides similarly corresponded to Abeta ratios in those with AD. Eventually, IASNTQSR, VAELEDEK, and VVSSIEQK were significantly associated with CDR, ADAS-11, and ADAS-13, particularly in MCI group. CONCLUSION: Our research suggests potential early diagnostic and prognostic utilities for certain peptides extracted from CSF-targeted proteomics research. The ethical approval of ADNI is available at ClinicalTrials.gov with Identifier: NCT00106899.