Association of CSF CD40 levels and synaptic degeneration across the Alzheimer's disease spectrum.

The CD40 pathway has been implicated in microglial activation, which is considered as a key factor in the pathogenesis of Alzheimer's disease (AD). However, the association of CSF CD40 and synaptic degeneration in living human is not clear. A total of 294 subjects with different severities of cognitive impairments were included in this study: 84 participants with normal cognition, 143 patients with mild cognitive impairment (MCI) and 67 patients with mild AD. Levels of CD40 in CSF were compared among the three groups. Further, several linear regression models were conducted to explore the associations of CSF CD40 and neurogranin levels (reflecting synaptic degeneration) when controlling for age, gender, educational attainment, APOE4 genotype, clinical diagnosis, CSF Aβ42 and tau proteins. We found that CSF CD40 levels were significantly decreased in patients with mild AD compared with healthy controls and MCI patients (control vs. AD, p = 0.0026; MCI vs. AD, p = 0.0268). However, there were no significant differences in CSF CD40 levels between controls and patients with MCI (p = 0.37). In addition, CSF CD40 levels were associated with neurogranin in the pooled sample when controlling for age, gender, educational attainment, APOE4 genotype and diagnosis. In summary, our findings support the notion that the CD40 pathway may contribute to an important mechanism underlying synaptic degeneration in AD.