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bioRxiv · 10.1101/2025.04.09.647928

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

Sanagi, T.·Okumura, M.·Lin, Y.·Kanemura, S.·Moon, E.·Heo, Y.·Takahara, K.·Tsunematsu, T.·Lee, Y.-H.
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Abstract

Alzheimers disease (AD) is characterized by aggregation and deposition of the amyloid-beta (A{beta}) 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 A{beta} species in particular brain regions and its effect on sleep impairment remains unclear. Here, we investigated the effect of A{beta}1-40 (A{beta}40) and A{beta}1-42 (A{beta}42) amyloid fibrils on sleep/wakefulness and cortical oscillations in 3-month old wild-type mice. A{beta}42 aggregated faster and demonstrated distinct structural properties compared with A{beta}40. Bilateral injections into the dentate gyrus of the hippocampus showed that A{beta}42 amyloid fibrils significantly disrupted sleep and cortical activity as well as caused neuronal death, whereas A{beta}40 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 A{beta}40 and A{beta}42 aggregates.

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Sanagi, T., Okumura, M., Lin, Y., Kanemura, S., Moon, E., Heo, Y., Takahara, K., Tsunematsu, T., Lee, Y.-H.. 2025-04-15. Amyloid fibrils in Alzheimer's disease differently modulate sleep and cortical oscillations in mice depending on the type of amyloid. https://doi.org/10.1101/2025.04.09.647928

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