Central Autonomic Dysfunction and Plasma Ab_42/40

Abstract Background Higher order regulation of autonomic function is maintained by cortical and subcortical interconnected regions within the brain, collectively referred to as the central autonomic network (CAN) (Benarroch, 1993). Despite the well‐established relationship between autonomic dysfunction and AD (Femminella et al., 2014) the relationship between CAN functional connectivity and biomarkers of AD, such as Ab 42/40 ratio, remains unexplored. Methods 76 independently living older adults were recruited from the community to undergo brain fMRI and venipuncture. Study exclusions were history of clinical stroke, dementia, major neurological or psychiatric disorder, current organ failure or other uncontrolled systemic illness. Resting state fMRI data were acquired and analyzed to quantify CAN functional connectivity from 3 previously described CAN networks with the CONN Functional Toolbox (Nieto‐Castanon, 2020). Default mode network connectivity was also included for analysis as a negative control. Plasma Aβ 40 and Aβ 42 concentrations were obtained by digital immunoassay with the Simoa Neurology 3‐Plex A (N3PA) Advantage Kit (Quanterix). Vascular risk factors were evaluated through interviews with the participant and informant, and included history of cardiovascular disease, hypertension, hyperlipidemia, type 2 diabetes, atrial fibrillation, and transient ischemic attack. The relationship between CAN functional connectivity and plasma Ab 42/40 ratio was compared using linear regression adjusting for demographic covariates and vascular risk factor burden. Results CAN functional connectivity was positively associated with Ab 42/40 for all three CAN models (CAN A (Beissner et al., 2013) P= .0001; CAN B (Monroe et al., 2020) P= .018; CAN C (Riganello et al., 2018) P= .006), and remained so after adjustment for age, sex, and vascular risk factor burden. Default mode network connectivity was not significantly associated with Ab 42/40 (Figure 1). Conclusion Older adults with decreased central autonomic network connectivity exhibit lower plasma Ab 42/40 , indicating greater cerebral Ab 1‐42 retention. This correlation could not be accounted for by age, sex, or vascular risk factor burden, suggesting a direct relationship between central autonomic function and cerebral amyloidosis. Further studies should explore the implications of CAN dysfunction for autonomic changes during the early stages of AD pathophysiology.