Association of Aortic Stiffness With Biomarkers of Neuroinflammation, Synaptic Dysfunction, and Neurodegeneration

Abstract

Objectives:To test the hypothesis that increased aortic stiffening is associated with greater cerebrospinal fluid (CSF) evidence of core Alzheimer’s disease pathology (Aβ, 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 Aβ, p-tau, t-tau, neurogranin, NFL, YKL-40, and sTREM2 concentrations adjusting for age, race/ethnicity, education, apolipoprotein (APOE) ε4 status, Framingham Stroke Risk Profile, and cognitive diagnosis. Models were repeated testing PWV interactions with age, diagnosis, APOE-ε4, and hypertension on each biomarker.Results:146 participants were examined (72±6 years). Aortic PWV interacted with age on p-tau (β=0.31, p=0.04), t-tau, (β=2.67, p=0.05), neurogranin (β=0.94, p=0.04), and sTREM2 (β=20.4, p=0.05). Among participants over age 73 years, higher aortic PWV related to higher p-tau (β=2.4, p=0.03), t-tau (β=19.3, p=0.05), neurogranin (β=8.4, p=0.01), and YKL-40 concentrations (β=7880, p=0.005). Aortic PWV had modest interactions with diagnosis on neurogranin (β=-10.76, p=0.03) and hypertension status on YKL-40 (β=-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.

Neurofilament light is associated with clinical outcome and hemorrhagic transformation in moderate to severe ischemic stroke

“…However, NFL did not meet statistical significant. 29 Leaving a question, whether NFL could be an independent factor to predict HT or not?…”

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia

“…Arterial stiffness significantly predicts cognitive decline [ 53 , 54 , 55 , 56 , 57 , 58 ] and incident dementia [ 59 ]. Arterial stiffness is also associated with multiple forms of dementia-related pathology, including WML volume, cerebral microbleeds, amyloid-β deposition in the brain, phosphorylated tau, and neuroinflammation in the cerebral spinal fluid [ 60 , 61 , 62 , 63 ]. We recently conducted a systematic review and meta-analysis of eight RCTs of soy isoflavones on arterial stiffness [ 64 ].…”

From Neurodevelopmental to Neurodegenerative Disorders: The Vascular Continuum

“…However, mice treated with VEGF have been shown to live longer, with extended multiorgan functionality (Grunewald et al, 2021). Furthermore, aging is associated with several vascular changes including aortic stiffness which has been linked to reduced blood flow in tissues leading to increased neuroinflammation and neurodegeneration later in life (Moore et al, 2021). Therefore, age-related changes in key vascular features may predispose to age-associated diseases (Banks et al, 2021).…”