| Abstrakt: |
Background: Aging is characterized by increased neuroinflammation, which plays an early role in the etiology of Alzheimer's disease (AD) (1) and cognitive decline (2). Cytokines play key roles in neuroinflammation in aging. We investigated whether levels of cerebrospinal fluid (CSF) interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) were associated with cognitive and brain decline and whether this relationship was mediated by baseline levels of CSF beta‐amyloid (Aβ‐42) and phosphorylated tau (p‐tau). Finally, we tested whether baseline IL‐6 and IL‐8 were related to changes in core AD biomarkers over time. Method: 219 older adults (62‐91 years), with baseline CSF IL‐6 and IL‐8, were followed over time (up to 9.50 years) by collecting longitudinal structural MRI, cognitive, and CSF data (n = 140). Linear mixed models (LME) were used to assess the effect of IL‐6 and IL‐8 on hippocampal atrophy, entorhinal thinning, lateral ventricle expansion, memory performance, and core AD CSF change. False discovery rate (pFDR) correction was applied to the models. Result: Higher CSF IL‐8 levels at baseline were associated with better memory performance over time, specifically in the context of lower levels of p‐tau (t = ‐2.00, pFDR = 0.05) and p‐tau/Aβ‐42 ratio (t = ‐2.15, pFDR = 0.03, Figure 1), while higher baseline IL‐6 were related to less CSF p‐tau changes over time (t = ‐2.61, pFDR = 0.02, Figure 2a). At trend levels, higher IL‐8 was associated with decrements of CSF Aβ‐42 levels over time (t = ‐2.25, uncorrected p = 0.02, Figure 2b), while higher IL‐6 was related to faster hippocampal volume decline with higher p‐tau/Aβ‐42 ratio (t = ‐2.21, uncorrected p = 0.03, Figure 2c). Conclusion: IL‐6 and IL‐8 show a complex profile in cognitively healthy aging pointing towards a neuroprotective role, especially with lower levels of the pathological load. [ABSTRACT FROM AUTHOR] |
