VGF AQEE- and GGEE-peptides differentiate between dementia types.

Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders with overlapping clinical features, making differential diagnosis challenging. The AQEE and GGEE peptides, derived from the proVGF neuroprotein, have emerged as potential cerebrospinal fluid (CSF) biomarkers for dementia. Indeed, we previously observed a reduction in AQEE-10 levels using selected reaction monitoring (SRM) and GGEE levels using enzyme-linked immunosorbent assay (ELISA) in a cohort of DLB patients compared to both controls and AD patients. To better investigate the diagnostic utility of these peptides, we analyzed CSF samples from both the original cohort and a newly recruited cohort. The new cohort (cohort 1) included patients, from Ulm University Hospital, with Parkinson's disease dementia (PDD) and DLB (combined as PDD/DLB; n = 18), and AD (n = 19). The previously analyzed cohort (cohort 2), from the Amsterdam University Medical Center, included DLB (n = 44), AD (n = 20), and cognitively healthy controls (n = 22). AQEE-10 levels were quantified by multiple reaction monitoring (MRM) in cohort 1 and by ELISA in both cohorts. GGEE levels were measured by ELISA in cohort 1 to corroborate and extend previous findings. MRM-based analysis revealed a significant reduction of AQEE-10 levels in DLB compared to both controls and AD (p < 0.05; ROC-AUC: 78% and 82%, respectively). This finding was confirmed by ELISA, for both AQEE-10 and GGEE peptide levels, along with a positive correlation between their concentrations. These results support AQEE-10 and GGEE as promising peptide biomarkers for distinguishing DLB from other dementia.