Because testing for the molecular markers that predict future development of Alzheimer’s disease (AD) pathology is costly and invasive, researchers have increasingly focused on blood-based biomarkers, which could be a more realistic option for widespread screening. Prior research has linked obstructive sleep apnea (OSA), a recognized contributor to the pathophysiology of AD, with elevated levels of Aβ and tau proteins. However, knowledge of OSA’s relationship with plasma amyloid, tau, and markers of neuronal injury, which could provide better understanding of its role in AD pathology, is limited.
In a study published in Alzheimer’s Association, Omonigho Michael Bubu, MD, MPH, PhD, and colleagues examined whether OSA influences levels of Aβ40, Aβ42, Aβ42/Aβ40 ratio, t-tau, t-tau/Aβ42 ratio, and neurofilament light chain, both independently of and synergistically with amyloid burden. The researchers also evaluated whether combining OSA severity and plasma Aβ42/Aβ40 ratio improved the predictive power for diagnosing brain amyloidosis, through cerebrospinal fluid, and tau pathology.
Participants included 120 cognitively normal older adults from New York University sleep and aging studies from 2013 to 2021. The study team measured OSA severity using apnea/hypopnea index with 4% desaturation, while plasma Aβ40, Aβ42, tau, and neurofilament light chain were measured using single molecule assay. Investigators measured cerebrospinal fluid amyloid and tau with enzyme-linked immunosorbent assay. Associations between these factors were evaluated using adjusted correlations and generalized models, while receiver-operating characteristic analyses were used to evaluate diagnostic accuracy.
Results showed that OSA severity was correlated with plasma Aβ40 (r=0.21), Aβ42 (r=0.26), and Aβ42/Aβ40 (r=0.20). Plasma tau and neurofilament light chain associations, meanwhile, depended on cerebrospinal fluid –Aβ42 levels. Researchers also found that OSA severity with Aβ42/Aβ40 improved amyloidosis (area under the curve [AUC]=0.78) and tau pathology (AUC=0.71) detection.
Overall, these findings show a link between OSA severity and elevated plasma Aβ, as well as elevated tau and neurofilament light chain with cerebrospinal fluid amyloid. This indicates that combined plasma and OSA measures could be used as non-invasive methods for detecting underlying brain amyloidosis and tau pathology, improving the identification of those at risk of developing AD.