Affiliation:
1. Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program Baltimore MD USA
2. SomaLogic Operating Co Boulder CO USA
3. Department of Neurology Johns Hopkins University School of Medicine Baltimore MD USA
4. Section of Biomedical Image Analysis, Department of Radiology University of Pennsylvania Philadelphia PA USA
5. Translational Gerontology Branch, National Institute on Aging, National Institutes of Health Baltimore MD USA
6. University of Mississippi Medical Center Jackson MS USA
7. Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA
8. Department of Medicine Columbia University Irving Medical Center New York NY USA
9. Department of Epidemiology Columbia Mailman School of Public Health New York NY USA
10. Department of Pediatrics, School of Medicine University of Colorado Anschutz Medical Campus Aurora CO USA
Abstract
ObjectiveFew studies have comprehensively examined how health and disease risk influence Alzheimer's disease (AD) biomarkers. The present study examined the association of 14 protein‐based health indicators with plasma and neuroimaging biomarkers of AD and neurodegeneration.MethodsIn 706 cognitively normal adults, we examined whether 14 protein‐based health indices (ie, SomaSignal® tests) were associated with concurrently measured plasma‐based biomarkers of AD pathology (amyloid‐β [Aβ]42/40, tau phosphorylated at threonine‐181 [pTau‐181]), neuronal injury (neurofilament light chain [NfL]), and reactive astrogliosis (glial fibrillary acidic protein [GFAP]), brain volume, and cortical Aβ and tau. In a separate cohort (n = 11,285), we examined whether protein‐based health indicators associated with neurodegeneration also predict 25‐year dementia risk.ResultsGreater protein‐based risk for cardiovascular disease, heart failure mortality, and kidney disease was associated with lower Aβ42/40 and higher pTau‐181, NfL, and GFAP levels, even in individuals without cardiovascular or kidney disease. Proteomic indicators of body fat percentage, lean body mass, and visceral fat were associated with pTau‐181, NfL, and GFAP, whereas resting energy rate was negatively associated with NfL and GFAP. Together, these health indicators predicted 12, 31, 50, and 33% of plasma Aβ42/40, pTau‐181, NfL, and GFAP levels, respectively. Only protein‐based measures of cardiovascular risk were associated with reduced regional brain volumes; these measures predicted 25‐year dementia risk, even among those without clinically defined cardiovascular disease.InterpretationSubclinical peripheral health may influence AD and neurodegenerative disease processes and relevant biomarker levels, particularly NfL. Cardiovascular health, even in the absence of clinically defined disease, plays a central role in brain aging and dementia. ANN NEUROL 2024;95:260–273
Funder
National Heart, Lung, and Blood Institute
Subject
Neurology (clinical),Neurology