Daniel A Nation1, Steven D Edland, Mark W Bondi, David P Salmon, Lisa Delano-Wood, Elaine R Peskind, Joseph F Quinn, Douglas R Galasko. 1. From the Veterans Affairs San Diego Healthcare System (D.A.N., M.W.B., L.D.-W.), San Diego; Departments of Neurosciences (S.D.E., D.P.S., D.R.G.) and Psychiatry (M.W.B., L.D.-W.), University of California, San Diego, La Jolla, CA; VA Puget Sound Health Care System (E.R.P.), Mental Illness Research, Education, and Clinical Center, Seattle; Departments of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle, WA; Department of Neurology (J.F.Q.), Oregon Health and Science University, Portland; and Portland VA Medical Center (J.F.Q.), Portland, OR.
Abstract
OBJECTIVE: The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including β-amyloid 1-42 (Aβ1-42) 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 Aβ1-42 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 Aβ1-42 (r = -0.19, p = 0.01), and increased P-tau to Aβ1-42 ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P-tau (β = 0.18, p = 0.0196) and P-tau to Aβ1-42 ratio (β = 0.0016, p < 0.001) but was no longer associated with Aβ1-42 (β = -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) (Aβ1-42: p = 0.050; P-tau: p = 0.003; P-tau to Aβ ratio: p = 0.0007) but not older participants (aged 70-100 years). CONCLUSIONS: PP elevation is associated with increased CSF P-tau and decreased Aβ1-42 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.
OBJECTIVE: The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including β-amyloid 1-42 (Aβ1-42) 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 Aβ1-42 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 Aβ1-42 (r = -0.19, p = 0.01), and increased P-tau to Aβ1-42 ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P-tau (β = 0.18, p = 0.0196) and P-tau to Aβ1-42 ratio (β = 0.0016, p < 0.001) but was no longer associated with Aβ1-42 (β = -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) (Aβ1-42: p = 0.050; P-tau: p = 0.003; P-tau to Aβ ratio: p = 0.0007) but not older participants (aged 70-100 years). CONCLUSIONS: PP elevation is associated with increased CSF P-tau and decreased Aβ1-42 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.
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