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Resting-state functional magnetic resonance imaging measures pathological alterations in neurodegenerative diseases, including Alzheimer’s disease. Disruption in functional connectivity may be a potential biomarker of ageing and early brain changes associated with AD-related genes, such as APOE and BDNF. The objective of this study was to identify group differences in resting-state networks between individuals with  BDNF  Val66Met and  APOE  polymorphisms in cognitively healthy older persons. Dual regression following Independent Components Analysis were performed to examine differences associated with these polymorphisms.  APOE  ε3 homozygotes showed stronger functional connectivity than  APOE  ε4 carriers. Males showed stronger functional connectivity between the Default Mode Network (DMN) and grey matter premotor cortex, while females showed stronger functional connectivity between the executive network and lateral occipital cortex and parahippocampal gyrus. Additionally, we found that with increasing cognitive reserve, functional connectivity increased within the Dorsal Attention Network (DAN), but decreased within the DMN. Interaction effects indicated stronger functional connectivity in Met/ε3 carriers than in Met/ε4 and Val/ε4 within both the DMN and DAN.  APOE / BDNF  interactions may therefore influence the integrity of functional brain connections in older adults, and may underlie a vulnerable phenotype for subsequent Alzheimer’s-type dementia.

Interactive effects of the APOE and BDNF polymorphisms on functional brain connectivity: the Tasmanian Healthy Brain Project