Plasma IL-12/IFN-γ axis predicts cognitive trajectories in cognitively unimpaired older adults

1. In the context of elevated amyloid-beta, IL-12p70 was associated with slower cognitive decline.

2. IFN-γ was associated with slower cognitive decline irrespective of amyloid-beta deposition.

Evidence Rating Level: 2 (Good)

It is currently understood that immune dysregulation, as well as premature immunosenescence and cytokine levels, impact the neurodegenerative process. Less understood, however, is the predictive value of cytokine levels in the context of cognitive trajectories in cognitively unimpaired individuals. This is particularly important among those who are amyloid-beta- (Aβ) positive. This longitudinal study assessed baseline plasma for nine cytokines of 298 cognitively unimpaired older adults (50 to 90 years old) to determine whether or not these biomarkers were associated with cognitive decline and Aβ deposition. Cytokine levels were also compared to Aβ and tau PET as well as neurodegeneration. Eligible participants had a score of 27 or greater on the age- and education-adjusted Mini Mental Status Examination and scored with the normatively average range on several other neuropsychological measures. Those with unstable medical or psychiatric conditions, as well as those with a stroke history, were excluded. Elevated IL-12p70 was found to be associated with slower cognitive decline in the context of increased Aβ (false discovery rate [FDR] = 0.0023). Conversely, IFN-γ was associated with cognitive decline irrespective of Aβ findings (FDR = 0.013). Elevated IL-12p70 was also associated with reduced neurodegeneration and tau protein in those with elevated Aβ. Overall, this study demonstrates the role of immune dysregulation in neurodegeneration, such that certain cytokines may serve a protective role in slowing cognitive decline in those with and without elevated Aβ.

Click to read the study in Alzheimer’s and Dementia

Image: PD

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