Indices of Arterial Stiffness and the Alzheimer’s Disease Biomarker, p-tau 217, in Non-demented Mid-life Women.

INTRODUCTION The association between indices of arterial stiffness and/or pressure wave reflection with Alzheimer disease amyloid-β accumulation and tau pathology in the brain is unclear. Deficiency of estrogen post-menopause may be an important contributor to changes in these indices to affect Alzheimer's disease progression. We aimed to assess the associations between indices of arterial stiffness and/or pressure wave reflection and the Alzheimer's disease blood biomarker, p-tau217 in mid-life women without dementia. METHODS This cross-sectional analysis of participants from the Integrated Women’s Health Program (IWHP), enrolled community-dwelling midlife women without dementia attending routine health screening at the National University Hospital in Singapore. Fasted blood p-tau217 was measured using the Simoa® ALZpath p-tau217 Advantage PLUS (Quanterix, MA, USA). Aortic augmentation index (AIx) and reflection index (RI) were obtained from peripheral arterial pressure waveforms, and cardio-ankle vascular index (CAVI) measured using pressure cuffs on the extremities and a phonocardiogram. Multivariable linear regression was used to examine the independent associations between indices of arterial stiffness and serum levels of p-tau217. RESULTS: Among 871 participants (mean age: 62.80 6.02 years), every SD increase in AIx and RI scores was both associated with 0.010 pg/mL (95% CI: 0.003 to 0.017, p=0.004) higher blood p-tau217 levels after adjustment for age, employment status, BMI, mild cognitive impairment, hypertension, cholesterol-HDL ratio, renal function, and ApoE4 carrier status. With natural logarithmic transformed p-tau217, RI remained significantly associated with ln(p-tau217), =0.026 (0.007, 0.045), p=0.007, after covariate adjustment. For AIx, the association was attenuated but remained directionally consistent. Trends for the association between CAVI and blood p-tau217 level were not statistically significant after adjustment for covariates. DISCUSSION Increases in indices of arterial stiffness and pressure wave reflection were associated with higher blood p-tau217 levels in community dwelling midlife women without dementia. These indices may be markers of risk for tau-related pathologies in the brain.