Association of aortic stiffness with biomarkers of neuroinflammation, synaptic dysfunction, and neurodegeneration

Objectives: To test the hypothesis that increased aortic stiffening is
associated with greater cerebrospinal fluid (CSF) evidence of core
Alzheimer’s disease pathology (Ab, phosphorylated tau (p-tau)),
neurodegeneration (total tau (t-tau)), synaptic dysfunction (neurogranin),
neuroaxonal injury (neurofilament light (NFL)), and neuroinflammation
(YKL-40, sTREM2), we analyzed pulse wave velocity (PWV) data and CSF data
among older adults. Methods: Participants free of stroke and dementia from
the Vanderbilt Memory and Aging Project, an observational community-based
study, underwent cardiac magnetic resonance to assess aortic pulse wave
velocity (PWV, m/sec) and lumbar puncture to obtain CSF. Linear
regressions related aortic PWV to CSF Ab, p-tau, t-tau, neurogranin, NFL,
YKL-40, and sTREM2 concentrations adjusting for age, race/ethnicity,
education, apolipoprotein (APOE) e4 status, Framingham Stroke Risk
Profile, and cognitive diagnosis. Models were repeated testing PWV
interactions with age, diagnosis, APOE-e4, and hypertension on each
biomarker. Results: 146 participants were examined (72±6 years). Aortic
PWV interacted with age on p-tau (b=0.31, p=0.04), t-tau, (b=2.67,
p=0.05), neurogranin (b=0.94, p=0.04), and sTREM2 (b=20.4, p=0.05). Among
participants over age 73 years, higher aortic PWV related to higher p-tau
(b=2.4, p=0.03), t-tau (b=19.3, p=0.05), neurogranin (b=8.4, p=0.01), and
YKL-40 concentrations (b=7880, p=0.005). Aortic PWV had modest
interactions with diagnosis on neurogranin (b=-10.76, p=0.03) and
hypertension status on YKL-40 (b=-18020, p<0.001). Conclusions:
Among our oldest participants, age 74 years and older, greater aortic
stiffening is associated with in vivo biomarker evidence of
neuroinflammation, tau phosphorylation, synaptic dysfunction, and
neurodegeneration, but not amyloidosis. Central arterial stiffening may
lead to cumulative cerebral microcirculatory damage and blood flow
delivery to tissue, resulting in neuroinflammation and neurodegeneration
in more advanced age.