Journal Article

Central autonomic network dysfunction and plasma Alzheimer’s disease biomarkers in older adults

Gaubert, Aimee, Mather, Mara, Bradford, David, Sordo, Lorena, Lohman, Trevor, Thayer, Julian F., Alitin, John Paul M., Engstrom, Allison C., Shenasa, Fatemah, Kapoor, Arunima, Nation, Daniel A., Rodgers, Kathleen E., Han, S. Duke, Head, Elizabeth

2024

Overview

Background Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer’s disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. Methods Independently living older adults ( N  = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ 42 , Aβ 40 ), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E ( APOE ) genotype. Interactive effects with APOE4 carrier status were also assessed. Results All autonomic networks were positively associated with Aβ 42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE 4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations ( B  = 910.00, P  = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. Conclusion The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ 42/40 , indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Advertising executives / Aged / Aged, 80 and over / Alzheimer Disease - blood / Alzheimer Disease - diagnostic imaging / Alzheimer Disease - physiopathology / Alzheimer's disease / Amyloid beta-Peptides - blood / Amyloidosis / Analysis / Apolipoproteins / Autonomic Nervous System - physiopathology / Autonomic Nervous System Diseases - blood / Autonomic Nervous System Diseases - etiology / Autonomic Nervous System Diseases - physiopathology / Aβ42/40 / Biological markers / Biomarkers - blood / Biomedical and Life Sciences / Biomedicine / Brain - diagnostic imaging / Brain - physiopathology / Central autonomic network / Female / Geriatric Psychiatry / Geriatrics/Gerontology / Glial fibrillary acidic protein / Glial Fibrillary Acidic Protein - blood / Health aspects / Humans / Magnetic Resonance Imaging / Male / Mental illness / Neurofilament light chain / Neurofilament Proteins - blood / Neurology / Neurosciences / Peptide Fragments - blood / Physiological aspects