Quantitative correlation between extracellular matrix protein degradation and the progression of neurodegeneration in Alzheimer's disease

BackgroundThe extracellular matrix (ECM) supports synaptic connections. Breakdown of ECM net component perineuronal nets (PNN) loses synaptic plasticity and causes the symptoms of neurological disorder like Alzheimer's diseases (AD).ObjectiveThis study analyzed PNN proteins and Tenascin-C (TNC), in the blood of AD, mild cognitive impairment (MCI) patients, and geriatric controls (GC), with correlation with tau and p-tau levels.MethodsThis case control study included 77 AD, 53 MCI patients, and 51 GC. Serum PNN and TNC levels were measured by surface plasmon resonance (SPR) method and validated by western blot. Statistical analyses included Kruskal-Wallis, logistic regression, Spearman correlation and receiver operating curve.ResultsPNN proteins and TNC were significantly elevated in AD compared to MCI and GC. Aggrecan and versican showed strong discriminatory power for AD from MCI, while TNC distinguished MCI from GC, indicating its potential for early detection of cognitive decline. Higher protein levels correlated with lower cognitive scores. Western blot result was consistent with SPR findings.ConclusionsThese results emphasize the significance of ECM proteins as biomarkers for cognitive impairments, showcasing their diverse diagnostic capabilities for AD. These findings provide further support for the involvement of PNN proteins in the pathophysiology of AD during early stage.