Amyloid fibrils in Alzheimer’s disease differently modulate sleep and cortical oscillations in mice depending on the type of amyloid

Alzheimer’s disease (AD) is characterized by aggregation and deposition of the amyloid-beta (Aβ) protein in patient brains, with aging playing a crucial role through oxidative stress and neuroinflammation. Sleep disturbances are common in patients with AD, and contribute to their cognitive impairment. However, the association between the aggregation of specific Aβ species in particular brain regions and its effect on sleep impairment remains unclear. Here, we investigated the effect of Aβ1–40 (Aβ40) and Aβ1–42 (Aβ42) amyloid fibrils on sleep/wakefulness and cortical oscillations in 3-month old wild-type mice. Aβ42 aggregated faster and demonstrated distinct structural properties compared with Aβ40. Bilateral injections into the dentate gyrus of the hippocampus showed that Aβ42 amyloid fibrils significantly disrupted sleep and cortical activity as well as caused neuronal death, whereas Aβ40 amyloid fibrils mainly affected cortical oscillations and caused minimal neuronal death. These findings shed light on AD-associated sleep disorders, which are differentially affected by the distinct properties of Aβ40 and Aβ42 aggregates.