Pregnancy hypertension is associated with higher p-tau217 in healthy midlife women.

Introduction: There is very limited knowledge on the relationship between pregnancy hypertension and the occurrence of pre-clinical Alzheimer's disease (AD).

Methods: Community-dwelling midlife women without dementia were enrolled from well-woman clinics of the National University Hospital, Singapore. Sociodemographic parameters and history of pregnancy hypertension were obtained. Cognition was assessed using the Montreal Cognitive Assessment-Basic tool. Fasted blood samples were stored for batched analysis of renal function, APOE genotyping and p-tau217 levels using Simoa® ALZpath p-tau217 Advantage PLUS (Quanterix, MA, USA). General linear modelling was used to examine the association between pregnancy hypertension and p-tau217.

Results: Among 743 women (mean age 62.9 ± 6.0; range: 50.7 to 76.6 years) enrolled, 68 (9.2%) reported pregnancy hypertension. General linear modelling showed that an older age [mean difference: 0.002 (95% CI: 0.001, 0.003)], mild cognitive impairment [0.016 (0.001, 0.032)], lower BMI [0.068 (0.027, 0.109)], eGFR<60 mL/min/1.73 m² [0.132 (0.072, 0.193)] and the APOE4 carrier genotype [0.038 (0.018, 0.058)] were independently associated with higher serum p-tau217 levels. History of pregnancy hypertension remained significantly associated with subsequent higher serum p-tau217 [0.040 (0.013, 0.067)], after adjustment for age, mild cognitive impairment, hypertension, BMI, renal function, and APOE4 genotype status.

Discussion: Pregnancy hypertension was associated with AD pathology with mean differences similar to high risk APOE4 carrier genotypes. Information on pregnancy hypertension could help physicians to identify women who might benefit from early p-tau217 screening for Alzheimer's disease, allowing for early clinical intervention.