Low frequency blood-oxygen-level-dependent oscillations, APOE4, and plasma pTau ₂₁₇

Background Low frequency oscillations in blood-oxygen-level-dependent signal (BOLD-LFOs) are generally considered nuisance signal in connectivity analysis and discarded. However, recent evidence suggests BOLD-LFOs shed light on cerebrovascular dysfunction and preclinical Alzheimer's disease, but the mechanisms remain unclear. No investigations have assessed the relationship between BOLD-LFOs and plasma pTau 217 , or how it differs in apolipoprotein ε4 ( APOE4 ) carriers who are vulnerable to cerebrovascular dysfunction and genetically predisposed to AD. Objective To study the relationship between BOLD-LFOs and plasma p-Tau 217 in APOE4 carriers compared to non-carriers. Methods Independently living older adults (N = 118) were recruited and underwent resting-state fMRI and venipuncture. BOLD-LFOs were quantified as signal power within the 0.01–0.10 Hz frequency range. Plasma pTau 217 was assessed and linear regression quantified the interactive effect of APOE4 carrier status and BOLD-LFOs on plasma pTau 217 . 2×2 ANCOVA was used to compare BOLD-LFOs across APOE4 carrier and amyloid positivity statuses based on previously reported pTau 217 cutoffs. Results The interactive effect of APOE4 carrier status and BOLD-LFO power was significantly associated with plasma pTau 217 (β = -0.78, p = 0.001). This relationship was driven by an inverse relationship between BOLD-LFOs and plasma pTau 217 in APOE4 carriers (β = −0.57, p = 0.0007). Amyloid-β (+) APOE4 carriers displayed lower BOLD-LFOs than amyloid-β (-) APOE4 carriers (p = 0.008) and amyloid-β (+) non-carriers (p = 0.03). Models were adjusted for age, sex, vascular risk factors, and total intracranial volume. Conclusions Findings suggests BOLD-LFOs are implicated in preclinical AD in an APOE4 dependent manner, adding support for the continued study of BOLD-LFOs in the context of cerebrovascular contributions to AD genetic risk.