Cerebrospinal fluid levels of tumour necrosis factor-α and its receptors are not associated with disease progression in Alzheimer’s disease

Introduction: Tumour necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in the regulation of innate and adaptive immunity. Two receptors exist for TNF-α: TNF receptors 1 (TNFR-1) and 2 (TNFR-2). TNFR-1 and TNFR-2 have been reported to be involved in pleiotropic functions. Multiple lines of evidence implicate TNF-α and its receptors as potential risk factors for Alzheimer’s disease (AD). Studies are warranted to assess the association of TNF-α, TNFR-1, and TNFR-2 with AD pathogenesis and whether they can serve as prognostic biomarkers indicative of AD. Methods: In the present study, baseline levels of cerebrospinal fluid (CSF) TNF-α, TNFR-1, and TNFR-2 were explored, and their potential as biomarkers to differentiate between individuals who remain stable and those who experience disease progression over 10 years in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was assessed. The study also examined the correlation between baseline CSF proteins with established AD biomarkers, neuroimaging measures, and cognition. Results: Whilst the present study shows associations between baseline CSF levels of TNFs with AD biomarkers, the nature of the relationship is ambiguous. Discussion: The present study concludes that CSF TNFs do not serve as reliable or robust disease biomarkers of AD.