The ratio of aggregation-prone to non-aggregation-prone plasma tau and amyloid-beta species (p-tau181/np-tau181 and Aβ42/Aβ40) increases during sleep due to preferential glymphatic clearance of aggregation-prone forms, providing a biomarker signature that distinguishes clearance-driven from release-driven changes.

During sleep, the brain's cleaning system opens up wider channels between brain cells, allowing fluid to flow more freely and carry away sticky protein clumps. These clumps, which are more likely to form Alzheimer’s plaques, get cleared out faster than their looser, non-clumping versions. As a result, the blood shows a higher proportion of the sticky forms compared to the non-sticky ones. When a person is awake, brain cells release more of the looser proteins, which dilutes the ratio of sticky forms in the blood.