Neuroligin fragments as blood-based biomarkers for early detection of Alzheimer’s disease

Biomarkers for early detection of Alzheimer’s disease (AD) are essential for improving treatments. Fragments of the synaptic protein neuroligins (NLGNs) are released into the blood due to synaptic degeneration, which occurs in the early stages of AD. Using MS2-targeted mass spectrometry, we assessed the potential of NLGN fragments as blood-based biomarkers for amnestic mild cognitive impairment (aMCI), a prodromal stage of AD. We found higher blood levels of certain NLGN fragments in both aMCI and AD patients compared to healthy subjects and elderly with subjective cognitive disorder (SCD) from the CIMA-Q cohort. Within these same samples, the levels of Tau phosphorylated at various epitopes (pTau181, pTau217, and pTau231) were higher in AD subjects but not in aMCI individuals. Our results suggest that synaptic proteins such as NLGNs could serve as effective biomarkers for detecting the disease in its prodromal stage. This early detection could accelerate diagnosis, prevention, and therapeutic intervention before neurodegeneration leads to irreversible brain damage.