CCN1/Cyr61 associates with β-amyloid levels in human cerebrospinal fluids.

CCN1, also called Cyr61, is a secreted protein involved in diverse biological processes including senescence. While elevated in brains of Alzheimer's disease (AD) models and patients, CCN1/Cyr61 levels in cerebrospinal fluid (CSF) remain unclear. Using a high-sensitive quantification method, we analyzed CSF samples from 79 subjects (age: 77.7 ± 5.4 years [63-94], MMSE: 20.1 ± 5.9 [0-30]) who underwent CSF tap test. CCN1/Cyr61 showed strong associations with Aβ40 (r = 0.67), Aβ42 (r = 0.48), Aβ42/40 ratio (r = -0.53), and phospho-tau levels (r = 0.53) (all; p < 0.0001). CCN1/Cyr61 also moderately associated with glial markers, YKL-40, sTREM2, CD163, and a lymphatic endothelial marker, LYVE-1 (r ≈ 0.4). While these cellular markers also associated with Aβ and phospho-tau, effects were much weaker. Collectively, CCN1/Cyr61 is associated with Aβ species and p-tau in CSF. These associations are considerably stronger than those observed with typical glial or other cellular markers, providing a clue to understanding the link between senescence and AD pathology at the levels of fluid biomarkers.