Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults

Objective: The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including beta-amyloid 1-42 (A beta(1-42)) and phosphorylated tau (P-tau) protein, in cognitively normal older adults. Methods: One hundred seventy-seven cognitively normal, stroke-free older adult participants (aged 55-100 years) underwent blood pressure assessment for determination of PP (systolic - diastolic blood pressure) and lumbar puncture for measurement of CSF A beta(1-42) and P-tau. Pearson correlations and multiple linear regression, controlling for age, sex, APOE genotype, and body mass index, evaluated the relationship between PP and Alzheimer disease biomarkers. Results: PP elevation was associated with increased P-tau (r = 0.23, p = 0.002), reduced A beta(1-42) (r=-20.19, p = 0.01), and increased P-tau to A beta(1-42) ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P-tau (beta = 0.18, p = 0.0196) and P-tau to A beta(1-42) ratio (beta = 0.0016, p < 0.001) but was no longer associated with A beta(1-42) (beta = -0.1, p = 0.35). Post hoc multivariate analyses indicated that increased PP was associated with all biomarkers in younger participants (aged 55-70 years) (A beta(1-42): p = 0.050; P-tau: p = 0.003; P-tau to A beta ratio: p = 0.0007) but not older participants (aged 70-100 years). Conclusions: PP elevation is associated with increased CSF P-tau and decreased Ab1-42 in cognitively normal older adults, suggesting that pulsatile hemodynamics may be related to amyloidosis and tau-related neurodegeneration. The relationship between PP and CSF biomarkers is age-dependent and observed only in participants in the fifth and sixth decades of life.