Mechanisms of Sleep Spindle-Mediated Memory Dysfunction in Alzheimer's Disease and Clinical Translation Directions

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss. AD is the most common type of dementia, accounting for about 60% to 80% of all dementia cases. Typical pathological features include extracellular β -amyloid protein (Aβ) deposition to form senile plaques, and intracellular hyperphosphorylated tau protein aggregation to form neurofibrillary tangles, and these pathological changes usually begin decades before clinical symptoms appear. More and more evidence shows that sleep disorder appears in the prodromal stage of AD. Sleep spindle wave during NREM sleep is an important electrophysiological oscillation, which is helpful to memory consolidation. This paper systematically integrates the existing research evidence, links the dysfunction of sleep spindle wave with cognitive decline, and introduces the physiological generation of sleep spindle wave and its core role in memory consolidation. We further summarized the characteristic decrease of fast spindle density, duration and σ power in patients with mild cognitive impairment and Alzheimer's disease, and clarified how Aβ deposition, tau protein pathology and neuroinflammation interfere with thalamic-cortical circuits, thus causing spindle abnormalities. In addition, this paper also introduces the experimental neural regulation strategy for sleep spindle. This study emphasized the transformation potential of sleep spindle as a non-invasive early biomarker, and provided theoretical support for developing a new dry pre-target for sleep-related Alzheimer's disease.