Low frequency blood-oxygen-level-dependent oscillations, APOE4, and plasma pTau₂₁₇

BackgroundLow 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 pTau₂₁₇, or how it differs in apolipoprotein ε4 (APOE4) carriers who are vulnerable to cerebrovascular dysfunction and genetically predisposed to AD.ObjectiveTo study the relationship between BOLD-LFOs and plasma p-Tau₂₁₇ in APOE4 carriers compared to non-carriers.MethodsIndependently 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 pTau₂₁₇ was assessed and linear regression quantified the interactive effect of APOE4 carrier status and BOLD-LFOs on plasma pTau₂₁₇. 2×2 ANCOVA was used to compare BOLD-LFOs across APOE4 carrier and amyloid positivity statuses based on previously reported pTau₂₁₇ cutoffs.ResultsThe interactive effect of APOE4 carrier status and BOLD-LFO power was significantly associated with plasma pTau₂₁₇ (β = -0.78, p = 0.001). This relationship was driven by an inverse relationship between BOLD-LFOs and plasma pTau₂₁₇ 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.ConclusionsFindings 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.