摘要 : Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined. Objective:... 展开 Background: Age-related cerebrovascular and neuroinflammatory processes have been independently identified as key mechanisms of Alzheimer's disease (AD), although their interactive effects have yet to be fully examined. Objective: The current study examined 1) the influence of pulse pressure (PP) and inflammatory markers on AD protein levels and 2) links between protein biomarkers and cognitive function in older adults with and without mild cognitive impairment (MCI). Methods: This study included 218 ADNI (81 cognitively normal [CN], 137 MCI) participants who underwent lumbar punctures, apolipoprotein E (APOE) genotyping, and cognitive testing. Cerebrospinal (CSF) levels of eight pro-inflammatory markers were used to create an inflammation composite, and amyloid-beta 1-42 (A beta(42)), phosphorylated tau (p-tau), and total tau (t-tau) were quantified. Results: Multiple regression analyses controlling for age, education, and APOE epsilon 4 genotype revealed significant PP x inflammation interactions for t-tau (B = 0.88, p = 0.01) and p-tau (B = 0.84, p = 0.02); higher inflammation was associated with higher levels of tau within the MCI group. However, within the CN group, analyses revealed a significant PP x inflammation interaction for A beta(42) (B = -1.01, p = 0.02); greater inflammation was associated with higher levels of A beta(42) (indicative of lower cerebral amyloid burden) in those with lower PP. Finally, higher levels of tau were associated with poorer memory performance within the MCI group only (ps < 0.05). Conclusion: PP and inflammation exert differential effects on AD CSF proteins and provide evidence that vascular risk is associated with greater AD pathology across our sample of CN and MCI older adults. 收起