CSF Biomarkers of Inflammation Are Predictive of Cognitive Decline

Analysis of study results presented at the American Academy of Neurology (AAN) 2024 Annual Meeting demonstrate that cerebrospinal fluid (CSF) inflammatory cytokine levels are predictive of clinically meaningful cognitive decline (CMCD) at 1 year follow up. TGF-β3 and TNFR2 were shown to be the strongest predictors of CMCD. According to the study authors, the added value of these biomarkers derives from their potential for predicting cognitive decline when used in addition to Alzheimer disease (AD)-specific biomarkers, such as amyloid beta (Aβ) and phosphorylated tau (p-tau).

The study included 242 older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), of whom 66 had dementia, 111 had mild cognitive impairment (MCI), and 65 were cognitively normal (CN). The primary outcome measured was CMCD as defined by a ≥4 increase on the Alzheimer’s Disease Assessment Scale Cognitive Subscore 11(ADAS-11). Researchers used machine learning models to assess the predictive performance of variables including demographics, APOE4 status, apolipoprotein E ε4 (APOE ε4) status, and CSF biomarkers of Aβ, p-tau, and inflammation.

The 11 inflammatory cytokines assessed included:

• TNFα
• TNFR1
• TNFR2
• TGFβ1
• TGFβ2
• TGFβ3
• IL6
• IL7
• IL10
• IL21
• ICAM1

After 1 year, CMCD was present in 25.6% of the study participants. The inflammatory biomarkers with the highest variable importance for predicting CMCD were as follows:

• TGFβ3 (0.522)
• TNFR2 (0.411)
• IL7 (0.227)
• ICAM1 (0.179)
• TNFα (0.147)

The authors of this study are affiliated with the Albert Einstein College of Medicine and the University of California, Irvine.