Low frequency BOLD oscillations, APOE4, and plasma pTau217

Background: Intrinsic low frequency oscillations in BOLD signal (BOLD LFOs) are generally considered nuisance signal in connectivity analysis and discarded. However, recent evidence suggests BOLD LFOs may shed light on cerebrovascular dysfunction and early Alzheimers disease pathophysiology, but the mechanisms remain unclear. No investigations to date have assessed the relationship between BOLD LFOs and plasma pTau217, or how this relationship differs in apolipoprotein e4 (APOE4) carriers who are vulnerable to cerebrovascular dysfunction and genetically predisposed to AD pathophysiology. Methods: Independently living older adults (N=118) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain functional MRI and venipuncture. Total BOLD LFOs were quantified as signal power within the 0.01 to 0.10 Hz frequency range. Plasma level of pTau217 was assessed and linear regression was used to quantify the interactive effect of APOE4 carrier status and BOLD LFOs on plasma pTau217. 2x2 ANCOVA was used to compare BOLD LFOs across APOE4 carrier and amyloid positivity statuses based on previously reported pTau217 cutoffs. Results: The interactive effect of APOE4 carrier status and BOLD LFO power was significantly associated with plasma pTau217 (β=-.65, p=.004). This relationship was driven by an inverse relationship between BOLD LFOs and plasma pTau217 in APOE4 carriers (β=-.49, p=.003). Amyloidβ positive APOE4 carriers displayed lower BOLD LFOs than amyloidβ negative APOE4 carriers (p=.02) and amyloid-β positive APOE4 non carriers (p=.04). All models were adjusted for age and sex. Conclusion: Present study findings suggests that BOLD LFOs are implicated early in AD pathophysiology in an APOE4 dependent manner, adding support for the continued study of BOLD LFOs in the context of cerebrovascular contributions to AD genetic risk.