Beat-to-beat blood pressure variability and Alzheimers disease pathophysiology
Preprint
Abstract
Introduction: Elevated blood pressure variability (BPV) is predictive of Alzheimers disease neuropathologic change observed with AD biomarkers. However, prior studies have largely focused on visit-to-visit BPV, which may be influenced by antihypertensive medication adherence and other external factors. Few studies have investigated beat-to-beat BPV, a reliable and direct measure of cardiovascular and autonomic function relevant to AD. Methods: Independently living older adults (N=132) were recruited from the community. Participants underwent continuous blood pressure monitoring and venipuncture. Plasma p-Tau217, p-Tau181, GFAP, NfL, and amyloid-β42/40 ratio were assessed. Linear regression examined the relationship between beat-to-beat systolic BPV and plasma AD biomarkers with and without adjustment for age, sex, systolic blood pressure, and apolipoprotein E4 (APOE4) carrier status. Results: Elevated beat-to-beat BPV was associated with elevated plasma p-Tau217 (β=0.32, p=0.008), plasma p-Tau181 (β=0.22, p=0.05), and plasma GFAP (β=0.41, p=0.00001). Elevated BPV was not associated with plasma amyloid-β42/40 ratio or plasma NfL. Discussion: Increased beat-to-beat BPV is associated with increased Core 1 T1 biomarkers of phosphorylated and secreted AD tau in blood plasma (i.e., pTau217, pTau181), but not with amyloid-β42/40 ratio, a biomarker more exclusively indexing cerebral amyloid retention alone. Elevated BPV was also associated with higher plasma GFAP, a marker of astrocyte reactivity. These findings are consistent with prior studies relating visit-to-visit BPV to AD biomarkers, suggesting that intrinsic cardiovascular and/or autonomic factors underlie links between BPV and AD.Funding Information
- Southern California Clinical and Translational Science Institute (KL2TR001854)