From Animal Models to At-Home Monitoring: The Translational Potential of Sleep Spindles as Non-invasive Biomarkers for Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is becoming more common and putting serious pressure on global health. Current Amyloid-β (Aβ) deposition and tau protein hyperphosphorylation are two main biomarkers of AD. Clinical diagnostic approaches depend on invasive detection of amyloid-β (Aβ) deposition and tau protein hyperphosphorylation through cerebrospinal fluid (CSF) analysis, positron emission tomography (PET) imaging or blood-based biomarker (BBM) testing. Evidence showed by recent studies have identified that slow-wave-sleep spindle coupling as potential non-invasive biomarkers of neurodegeneration for AD patients. Yet, the causality between spindle disruption and cognitive decline remains unknown. This paper examines the evidences from human, rodent models, and nonhuman primate (NHP) models of recent studies. This study presents how slow wave-spindle coupling reflects prefrontal-hippocampal, thalamocortical function. And it evaluates the contributions of NHPs researches for understanding the causal mechanisms. The findings provide supportive evidence that slow-wave-spindle activity is a reliable marker of thalamocortical integrity and prefrontal-hippocampal function correlating with cognitive decline for AD. Study shows the non-rapid eye movement (NREM) spindle and slow oscillation (SO) activity are predictive and non-invasive biomarkers for AD. The disruption of spindle-SO coupling is associated with Aβ deposits of AD. This predictive biomarker of AD points toward future directions for early detection and clinical interventions. These findings enable standardized predictive detection, home-based electroencephalography (EEG) monitoring and closed-loop stimulation techniques that could strengthen the clinical translation.