Developing Topics

Background: Current blood biomarkers of Alzheimer's disease (AD) neuropathology and neurodegeneration include the ratio of amyloid-β 42 to 40 (Aβ42/Aβ40), phosphorylated tau at threonine 181 (p-Tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Prior studies have reported that hypertension is cross-sectionally associated with lower levels of Aβ42/Aβ40 and longitudinally associated with faster accumulation of NfL. In this longitudinal investigation, we expanded on prior research by examining whether mid-life blood pressure status was associated with change in AD biomarkers from mid- to late-life.

Method: In the Atherosclerosis in Communities Study (ARIC) cohort, 1424 participants had blood pressure measurements at Visit 3 (baseline, 1993-95) and two or more measurements of AD blood biomarkers from Visit 3, Visit 5 (2011-13), and Visit 6 or 7 (2016-2019). Linear mixed effects models quantified the association of mid-life blood pressure status (hypotension, SBP<90 or DBP<60; hypertension, SBP>130 or DBP>90; normotension) with the rate of change in each AD blood biomarker. Models were adjusted for age, sex, race, education, the presence of apolipoprotein ε4 (APOE ε4) alleles, time-varying body mass index and estimated glomerular filtration rate, and baseline cardiovascular and lifestyle risk factors.

Result: The sample included 860 women (60.4%) and 364 Black participants (25.6%). At baseline, 143 participants (10.0%) had hypotension and 449 (31.5%) had hypertension. Compared to participants with normotension, mid-life hypertension was associated with accelerated accumulation of NfL from mid- to late-life (Table 2). Both mid-life hypotension and hypertension were associated with accelerated accumulation of pTau-181 from mid- to late-life. In subgroup analyses, these associations were greater among women, Black participants, and individuals without APOE ε4 alleles.

Conclusion: Mid-life hypotension and hypertension are associated with faster changes in both AD-specific (pTau-181) and neurodegenerative (NfL) biomarkers from midlife to late-life. Future investigation is needed to determine whether hypotension and hypertension are on the causal pathway relating AD neuropathology to dementia or if abnormal blood pressure and faster accumulation of pTau-181 are shared characteristics of other comorbidities.