Promoter haplotypes of interleukin-10 gene linked to cortex plasticity in subjects with risk of Alzheimer's disease

The Alzheimer's disease (AD) aetiologic event is associated with brain inflammatory processes. In this study, we consider a haplotype of the IL-10 gene promoter region, − 1082A/− 819 T/− 592A (ATA haplotype), which is an additive and independent genetic risk factor for AD. Episodic memory change is the most striking cognitive alteration in AD. It remains unclear whether episodic memory networks can be affected by the ATA haplotype variant in amnestic mild cognitive impairment (aMCI), and if so, how this occurs. Thirty-nine aMCI patients and 30 healthy controls underwent resting-state functional magnetic resonance imaging. An imaging genetics approach was then utilized to investigate disease-related differences in episodic memory networks between the groups based on ATA haplotype-by-aMCI interactions. Gene-brain-behaviour relationships were then further examined. This study found that the ATA haplotype risk variant was associated with abnormal functional communications in the hippocampus-frontoparietal cortices, especially in the left hippocampal network. Moreover, these ATA haplotype carriers showed a distinct phase of hyperactivity in normal aging, with rapid declines of brain function in aMCI subjects when compared to non-ATA haplotype carriers. These findings added to the accumulating evidence that promoter haplotypes of IL-10 may be important modulators of the development of aMCI.