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

Elizabeth E Moore; Dandan Liu; Judy Li; Samantha J Schimmel; Francis E Cambronero; James G Terry; Sangeeta Nair; Kimberly R Pechman; Marissa E Moore; Susan P Bell; Joshua A Beckman; Katherine A Gifford; Timothy J Hohman; Kaj Blennow; Henrik Zetterberg; John Jeffrey Carr; Angela L Jefferson

doi:10.1212/WNL.0000000000012257

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

Neurology. 2021 Jul 27;97(4):e329-e340. doi: 10.1212/WNL.0000000000012257. Epub 2021 May 24.

Authors

Elizabeth E Moore¹, Dandan Liu¹, Judy Li¹, Samantha J Schimmel¹, Francis E Cambronero¹, James G Terry¹, Sangeeta Nair¹, Kimberly R Pechman¹, Marissa E Moore¹, Susan P Bell¹, Joshua A Beckman¹, Katherine A Gifford¹, Timothy J Hohman¹, Kaj Blennow¹, Henrik Zetterberg¹, John Jeffrey Carr¹, Angela L Jefferson²

Affiliations

¹ From the Vanderbilt Memory & Alzheimer's Center (E.E.M., D.L., J.L., S.J.S., F.E.C., K.R.P., M.E.M., K.A.G., T.J.H., A.L.J.), Department of Biostatistics (D.L.), Radiology & Radiological Sciences (J.G.T., S.N., J.J.C.), Department of Neurology (K.R.P., M.E.M., K.A.G., T.J.H., A.L.J.), Division of Cardiovascular Medicine (S.P.B., J.A.B., A.L.J.), Department of Medicine, and Vanderbilt Genetics Institute (T.J.H.), Vanderbilt University Medical Center, Nashville, TN; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Molndal, Sweden; Department of Neurodegenerative Disease (H.Z.), University College London Institute of Neurology, Queen Square; and United Kingdom Dementia Research Institute at University College London (H.Z.), UK.
² From the Vanderbilt Memory & Alzheimer's Center (E.E.M., D.L., J.L., S.J.S., F.E.C., K.R.P., M.E.M., K.A.G., T.J.H., A.L.J.), Department of Biostatistics (D.L.), Radiology & Radiological Sciences (J.G.T., S.N., J.J.C.), Department of Neurology (K.R.P., M.E.M., K.A.G., T.J.H., A.L.J.), Division of Cardiovascular Medicine (S.P.B., J.A.B., A.L.J.), Department of Medicine, and Vanderbilt Genetics Institute (T.J.H.), Vanderbilt University Medical Center, Nashville, TN; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Molndal, Sweden; Department of Neurodegenerative Disease (H.Z.), University College London Institute of Neurology, Queen Square; and United Kingdom Dementia Research Institute at University College London (H.Z.), UK. angela.jefferson@vumc.org.

Abstract

Objectives: To test the hypothesis that increased aortic stiffening is associated with greater CSF evidence of core Alzheimer disease pathology (β-amyloid [Aβ], 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 Aβ, p-tau, t-tau, neurogranin, NFL, YKL-40, and sTREM2 concentrations after adjustment 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: One hundred forty-six participants were examined (age 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 >73 years of age, 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 = 7,880, 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 = 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Aging / cerebrospinal fluid
Aging / physiology*
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid
Female
Heart / diagnostic imaging*
Humans
Inflammation / diagnostic imaging*
Male
Middle Aged
Neurodegenerative Diseases / cerebrospinal fluid
Neurodegenerative Diseases / diagnostic imaging*
Phosphorylation
Pulse Wave Analysis
Vascular Stiffness / physiology*
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding