Emerging evidence suggests that sleep deprivation (SD) and circadian rhythm disruption (CRD) may interact and increase the risk for the development of Alzheimer's disease (AD). This review inspects different pathophysiological aspects of SD and CRD, and shows that the two may impair the glymphatic-vascular-lymphatic clearance of brain macromolecules (e.g., β-amyloid and microtubule associated protein tau), increase local brain oxidative stress and diminish circulatory melatonin levels. Lastly, this review looks into the potential association between sleep and circadian rhythm with stress granule formation, which might be a new mechanism along the AD pathogenic pathway. In summary, SD and CRD is likely to be associated with a positive risk in developing Alzheimer's disease in humans.