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 CSF evidence of core Alzheimer disease pathology (beta-amyloid [A beta], phosphorylated tau [p-tau]), neurodegeneration (total tau [t-tau]), synaptic dysfunction (neurogranin), neuroaxonal injury (neurofilament light [NFL]), and neuroinflammation (YKL-40, soluble triggering receptor expressed on myeloid cells 2 [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 PWV (meters per second) and lumbar puncture to obtain CSF. Linear regressions related aortic PWV to CSF A beta, p-tau, t-tau, neurogranin, NFL, YKL-40, and sTREM2 concentrations after adjustment for age, race/ethnicity, education, apolipoprotein (APOE) epsilon 4 status, Framingham Stroke Risk Profile, and cognitive diagnosis. Models were repeated testing PWV interactions with age, diagnosis, APOE epsilon 4, and hypertension on each biomarker. Results One hundred forty-six participants were examined (age 72 +/- 6 years). Aortic PWV interacted with age on p-tau (beta = 0.31, p = 0.04), t-tau, (beta = 2.67, p = 0.05), neurogranin (beta = 0.94, p = 0.04), and sTREM2 (beta = 20.4, p = 0.05). Among participants >73 years of age, higher aortic PWV related to higher p-tau (beta = 2.4, p = 0.03), t-tau (beta = 19.3, p = 0.05), neurogranin (beta = 8.4, p = 0.01), and YKL-40 concentrations (beta = 7,880, p = 0.005). Aortic PWV had modest interactions with diagnosis on neurogranin (beta = -10.76, p = 0.03) and hypertension status on YKL-40 (beta = 18,020, p < 0.001). Conclusions Among our oldest participants, >= 74 years of age, 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 reduced blood flow delivery to tissue, resulting in neuroinflammation and neurodegeneration in more advanced age.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

pulse-wave velocity

expert consensus document

arterial stiffness

alzheimers-disease

pressure

age

progression

relate

flow

sex

Neurosciences & Neurology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)